Trial Outcomes & Findings for A Randomized Trial of Medical and Surgical Treatments for Patients With GERD Symptoms That Are Refractory to Proton Pump Inhibitors (NCT NCT01265550)

Last Updated: 2020-01-22

Results Overview

Success; ≥50% improvement in the baseline GERD-HRQL score at 12 months. Failure; \<50% improvement in the baseline GERD-HRQL score at 12 months or: 1. For patients randomized to Surgical Treatment: a.\<50% improvement in the baseline GERD-HRQL score and/or persistent heartburn of sufficient severity to warrant treatment with any antisecretory medication, antireflux medication or neurotropic medication at any quarterly clinic visit. 2. For patients randomized to Active Medical or Placebo Medical Treatment: a.inability to tolerate both study medications or b.For patients treated with desipramine, i.\<50% improvement in baseline GERD-HRQL score symptom after at least 10 weeks of treatment with the second drug at any quarterly clinic visit. c.For patients in whom desipramine is contraindicated,i.\<50% improvement in baseline GERD-HRQL score symptom after at least 10 weeks of treatment with baclofen or its corresponding placebo at any quarterly clinic visit.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

366 participants

Primary outcome timeframe

12 months

Results posted on

2020-01-22

Participant Flow

Participant milestones

Participant milestones
Measure	Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	All Enrolled All patients consented.
Pre Randomization STARTED	0	0	0	366
Pre Randomization COMPLETED	0	0	0	78
Pre Randomization NOT COMPLETED	0	0	0	288
Post Randomization STARTED	25	27	26	0
Post Randomization COMPLETED	10	19	6	0
Post Randomization NOT COMPLETED	15	8	20	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	All Enrolled All patients consented.
Pre Randomization Withdrawal by Subject	0	0	0	70
Pre Randomization Technical Exclusions	0	0	0	54
Pre Randomization GERD, PPI-Responsive	0	0	0	42
Pre Randomization Non-GERD organic disorders	0	0	0	23
Pre Randomization Functional heartburn	0	0	0	99

Baseline Characteristics

Missing data

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Medical Treatment Group n=25 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group n=27 Participants Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group n=26 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Not Randomized n=288 Participants Subset of all enrolled participants who did not end up being randomized to the study.	Total n=366 Participants Total of all reporting groups
Age, Continuous	43.9 years STANDARD_DEVIATION 12.2 • n=25 Participants • Missing data	44.9 years STANDARD_DEVIATION 11.8 • n=27 Participants • Missing data	47.2 years STANDARD_DEVIATION 11.7 • n=26 Participants • Missing data	49.3 years STANDARD_DEVIATION 12.2 • n=280 Participants • Missing data	45.4 years STANDARD_DEVIATION 11.8 • n=358 Participants • Missing data
Sex: Female, Male Female	7 Participants n=25 Participants • Missing data.	4 Participants n=27 Participants • Missing data.	3 Participants n=26 Participants • Missing data.	63 Participants n=279 Participants • Missing data.	77 Participants n=357 Participants • Missing data.
Sex: Female, Male Male	18 Participants n=25 Participants • Missing data.	23 Participants n=27 Participants • Missing data.	23 Participants n=26 Participants • Missing data.	216 Participants n=279 Participants • Missing data.	280 Participants n=357 Participants • Missing data.
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=25 Participants • Missing data.	7 Participants n=27 Participants • Missing data.	2 Participants n=26 Participants • Missing data.	40 Participants n=279 Participants • Missing data.	53 Participants n=357 Participants • Missing data.
Ethnicity (NIH/OMB) Not Hispanic or Latino	21 Participants n=25 Participants • Missing data.	20 Participants n=27 Participants • Missing data.	23 Participants n=26 Participants • Missing data.	230 Participants n=279 Participants • Missing data.	294 Participants n=357 Participants • Missing data.
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=25 Participants • Missing data.	0 Participants n=27 Participants • Missing data.	1 Participants n=26 Participants • Missing data.	9 Participants n=279 Participants • Missing data.	10 Participants n=357 Participants • Missing data.
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=25 Participants • Missing data	0 Participants n=27 Participants • Missing data	0 Participants n=26 Participants • Missing data	3 Participants n=279 Participants • Missing data	3 Participants n=357 Participants • Missing data
Race (NIH/OMB) Asian	0 Participants n=25 Participants • Missing data	0 Participants n=27 Participants • Missing data	0 Participants n=26 Participants • Missing data	2 Participants n=279 Participants • Missing data	2 Participants n=357 Participants • Missing data
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=25 Participants • Missing data	0 Participants n=27 Participants • Missing data	1 Participants n=26 Participants • Missing data	0 Participants n=279 Participants • Missing data	1 Participants n=357 Participants • Missing data
Race (NIH/OMB) Black or African American	2 Participants n=25 Participants • Missing data	2 Participants n=27 Participants • Missing data	5 Participants n=26 Participants • Missing data	54 Participants n=279 Participants • Missing data	63 Participants n=357 Participants • Missing data
Race (NIH/OMB) White	20 Participants n=25 Participants • Missing data	17 Participants n=27 Participants • Missing data	17 Participants n=26 Participants • Missing data	183 Participants n=279 Participants • Missing data	237 Participants n=357 Participants • Missing data
Race (NIH/OMB) More than one race	2 Participants n=25 Participants • Missing data	2 Participants n=27 Participants • Missing data	2 Participants n=26 Participants • Missing data	16 Participants n=279 Participants • Missing data	22 Participants n=357 Participants • Missing data
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=25 Participants • Missing data	6 Participants n=27 Participants • Missing data	1 Participants n=26 Participants • Missing data	21 Participants n=279 Participants • Missing data	29 Participants n=357 Participants • Missing data

PRIMARY outcome

Timeframe: 12 months

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=25 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group n=27 Participants Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group n=26 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Participants Achieving at Least a 50% Improvement in the Gastroesophageal Reflux Disease Health-related Quality of Life Index (GERD-HRQL) From Baseline to 12 Months	7 Participants	18 Participants	3 Participants

SECONDARY outcome

Timeframe: Screening

Population: The Overall number of participants analyzed represents those Enrolled Participants who were evaluated for esophageal ulceration.

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=216 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Enrolled Participants With Esophageal Ulceration.	0 Participants	—	—

SECONDARY outcome

Timeframe: Screening

Population: The Overall number of participants analyzed represents those Enrolled Participants who were evaluated for reflux esophagus.

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=216 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Enrolled Participants With Reflux Esophagus.	4 Participants	—	—

SECONDARY outcome

Timeframe: Screening

Population: The Overall number of participants analyzed represents those Enrolled Participants who were evaluated for eosinophilic esophagitis

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=215 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Enrolled Participants With Eosinophilic Esophagitis	16 Participants	—	—

SECONDARY outcome

Timeframe: Screening

Population: The Overall number of participants analyzed represents those Enrolled Participants who were evaluated for active ulcerations of the stomach and/or duodenum

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=216 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Enrolled Participants With Active Ulceration of the Stomach and/or Duodenum.	3 Participants	—	—

SECONDARY outcome

Timeframe: Screening

Population: The Overall number of participants analyzed represents those Enrolled Participants who were evaluated for neoplasm of the esophagus, stomach or duodenum

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=216 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Enrolled Participants With Neoplasm of the Esophagus, Stomach or Duodenum	0 Participants	—	—

SECONDARY outcome

Timeframe: Screening

Population: The Overall number of participants analyzed represents those Enrolled Participants who were evaluated for candida esophagitis

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=216 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Enrolled Participants With Candida Esophagitis.	3 Participants	—	—

SECONDARY outcome

Timeframe: Screening

Population: The Overall number of participants analyzed represents those Enrolled Participants who were evaluated for gastric outlet obstruction

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=216 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Enrolled Participants With Gastric Outlet Obstruction	0 Participants	—	—

SECONDARY outcome

Timeframe: Screening

Population: The Overall number of participants analyzed represents those Enrolled Participants who were evaluated for achalasia

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=212 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Enrolled Participants With Achalasia	2 Participants	—	—

SECONDARY outcome

Timeframe: Screening

Population: The Overall number of participants analyzed represents those Enrolled Participants who were evaluated for aperistalsis

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=212 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Enrolled Participants With Aperistalsis	0 Participants	—	—

SECONDARY outcome

Timeframe: Screening

Population: The Overall number of participants analyzed represents those Enrolled Participants who were evaluated for distal esophageal spasm

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=212 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Enrolled Participants With Distal Esophageal Spasm	3 Participants	—	—

SECONDARY outcome

Timeframe: Screening

Population: The Overall number of participants analyzed represents those Enrolled Participants who were evaluated for nutcracker esophagus

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=32 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Enrolled Participants With Nutcracker Esophagus	2 Participants	—	—

SECONDARY outcome

Timeframe: Screening

Population: The Overall number of participants analyzed represents those Enrolled Participants who were evaluated for ineffective esophageal motility

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=33 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Enrolled Participants With Ineffective Esophageal Motility	1 Participants	—	—

SECONDARY outcome

Timeframe: Screening

Population: The Overall number of participants analyzed represents those Enrolled Participants who were evaluated for rapid contraction

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=93 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Enrolled Participants With Rapid Contraction	2 Participants	—	—

SECONDARY outcome

Timeframe: Screening

Population: The Overall number of participants analyzed represents those Enrolled Participants who were evaluated for hypertensive peristalsis

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=93 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Enrolled Participants With Hypertensive Peristalsis	3 Participants	—	—

SECONDARY outcome

Timeframe: Screening

Population: The Overall number of participants analyzed represents those Enrolled Participants who were evaluated for jackhammer esophagus

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=93 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Enrolled Participants With Jackhammer Esophagus	8 Participants	—	—

SECONDARY outcome

Timeframe: Screening

Population: The Overall number of participants analyzed represents those Enrolled Participants who were evaluated for weak peristalsis I

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=93 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Enrolled Participants With Weak Peristalsis I	10 Participants	—	—

SECONDARY outcome

Timeframe: Screening

Population: The Overall number of participants analyzed represents those Enrolled Participants who were evaluated for weak peristalsis II

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=93 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Enrolled Participants With Weak Peristalsis II	9 Participants	—	—

SECONDARY outcome

Timeframe: Screening

Population: The Overall number of participants analyzed represents those Enrolled Participants who were evaluated for anxiety and/or depression

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=272 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Enrolled Participants With Anxiety and/or Depression	125 Participants	—	—

SECONDARY outcome

Timeframe: Screening

Population: The Overall number of participants analyzed represents those Enrolled Participants who were evaluated for functional heartburn

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=274 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Enrolled Participants With Functional Heartburn	221 Participants	—	—

SECONDARY outcome

Timeframe: Screening

Population: The Overall number of participants analyzed represents those Enrolled Participants who were evaluated for functional chest pain of presumed esophageal origin

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=276 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Enrolled Participants With Functional Chest Pain of Presumed Esophageal Origin	13 Participants	—	—

SECONDARY outcome

Timeframe: Screening

Population: The Overall number of participants analyzed represents those Enrolled Participants who were evaluated for functional dysphagia

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=277 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Enrolled Participants With Functional Dysphagia	7 Participants	—	—

SECONDARY outcome

Timeframe: Screening

Population: The Overall number of participants analyzed represents those Enrolled Participants who were evaluated for globus

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=278 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Enrolled Participants With Globus	0 Participants	—	—

SECONDARY outcome

Timeframe: Screening

Population: The Overall number of participants analyzed represents those Enrolled Participants who were evaluated for belching disorders

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=273 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Enrolled Participants With Belching Disorders	130 Participants	—	—

SECONDARY outcome

Timeframe: Screening

Population: The Overall number of participants analyzed represents those Enrolled Participants who were evaluated for chronic idiopathic nausea

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=273 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Enrolled Participants With Chronic Idiopathic Nausea	51 Participants	—	—

SECONDARY outcome

Timeframe: Screening

Population: The Overall number of participants analyzed represents those Enrolled Participants who were evaluated for functional vomiting

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=276 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Enrolled Participants With Functional Vomiting	32 Participants	—	—

SECONDARY outcome

Timeframe: Screening

Population: The Overall number of participants analyzed represents those Enrolled Participants who were evaluated for cyclic vomiting syndrome

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=276 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Enrolled Participants With Cyclic Vomiting Syndrome	86 Participants	—	—

SECONDARY outcome

Timeframe: Screening

Population: The Overall number of participants analyzed represents those Enrolled Participants who were evaluated for irritable bowel syndrome

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=277 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Enrolled Participants With Irritable Bowel Syndrome	152 Participants	—	—

SECONDARY outcome

Timeframe: Screening

Population: The Overall number of participants analyzed represents those Enrolled Participants who were evaluated for functional bloating

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=277 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Enrolled Participants With Functional Bloating	8 Participants	—	—

SECONDARY outcome

Timeframe: Screening

Population: The Overall number of participants analyzed represents those Enrolled Participants who were evaluated for functional diarrhea

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=271 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Enrolled Participants With Functional Diarrhea	4 Participants	—	—

SECONDARY outcome

Timeframe: Screening

Population: The Overall number of participants analyzed represents those Enrolled Participants who were evaluated for unspecified functional bowel disorder

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=278 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Enrolled Participants With Unspecified Functional Bowel Disorder	56 Participants	—	—

SECONDARY outcome

Timeframe: Screening

Population: The Overall number of participants analyzed represents those Enrolled Participants who were evaluated for functional gallbladder disorder

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=278 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Enrolled Participants With Functional Gallbladder Disorder	1 Participants	—	—

SECONDARY outcome

Timeframe: 12 months

Population: Number of treatment successes.

Association between anxiety and/or depression (GAD-7 and PHQ-9) and the outcome of medical and surgical treatments (success or failure) will be evaluated.

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=7 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group n=18 Participants Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group n=3 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Successful Participants With Anxiety and/or Depression.	2 Participants	5 Participants	0 Participants

SECONDARY outcome

Timeframe: 12 months

Population: Number of treatment successes.

Presence of functional heartburn as assessed by the ROME III functional GI disorders questionnaire.

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=7 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group n=18 Participants Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group n=3 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Successful Participants With Functional Heartburn	7 Participants	14 Participants	3 Participants

SECONDARY outcome

Timeframe: 12 months

Population: Number of treatment successes.

Presence of functional chest pain of presumed esophageal origin as assessed by the ROME III functional GI disorders questionnaire.

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=7 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group n=18 Participants Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group n=3 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Successful Participants With Functional Chest Pain of Presumed Esophageal Origin	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 12 months

Population: Number of treatment successes.

Presence of functional dysphagia as assessed by the ROME III functional GI disorders questionnaire.

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=7 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group n=18 Participants Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group n=3 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Successful Participants With Functional Dysphagia	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 12 months

Population: Number of treatment successes.

Presence of globus as assessed by the ROME III functional GI disorders questionnaire.

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=7 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group n=18 Participants Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group n=3 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Successful Participants With Globus	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 12 months

Population: Number of treatment successes.

Presence of belching disorders as assessed by the ROME III functional GI disorders questionnaire.

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=7 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group n=18 Participants Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group n=3 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Successful Participants With Belching Disorders	3 Participants	12 Participants	2 Participants

SECONDARY outcome

Timeframe: 12 months

Population: Number of treatment successes.

Presence of chronic idiopathic nausea as assessed by the ROME III functional GI disorders questionnaire.

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=7 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group n=18 Participants Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group n=3 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Successful Participants With Chronic Idiopathic Nausea	0 Participants	3 Participants	0 Participants

SECONDARY outcome

Timeframe: 12 months

Population: Number of treatment successes.

Presence of functional vomiting as assessed by the ROME III functional GI disorders questionnaire.

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=7 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group n=18 Participants Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group n=3 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Successful Participants With Functional Vomiting	1 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: 12 months

Population: Number of treatment successes.

Presence of cyclic vomiting syndrome as assessed by the ROME III functional GI disorders questionnaire.

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=7 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group n=18 Participants Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group n=3 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Successful Participants With Cyclic Vomiting Syndrome	1 Participants	7 Participants	1 Participants

SECONDARY outcome

Timeframe: 12 months

Population: Number of treatment successes

Presence of irritable bowel syndrome as assessed by the ROME III functional GI disorders questionnaire.

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=7 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group n=18 Participants Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group n=3 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Successful Participants With Irritable Bowel Syndrome	3 Participants	10 Participants	3 Participants

SECONDARY outcome

Timeframe: 12 months

Population: Number of treatment successes.

Presence of functional bloating as assessed by the ROME III functional GI disorders questionnaire.

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=7 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group n=18 Participants Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group n=3 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Successful Participants With Functional Bloating	1 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: 12 months

Population: Number of treatment successes

Presence of functional diarrhea as assessed by the ROME III functional GI disorders questionnaire.

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=7 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group n=18 Participants Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group n=3 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Successful Participants With Functional Diarrhea	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 12 months

Population: Number of treatment successes.

Presence of unspecified functional bowel disorder as assessed by the ROME III functional GI disorders questionnaire.

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=7 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group n=18 Participants Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group n=3 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Successful Participants With Unspecified Functional Bowel Disorder	2 Participants	5 Participants	0 Participants

SECONDARY outcome

Timeframe: 12 months

Population: Number of treatment successes

Presence of functional gallbladder disorder as assessed by the ROME III functional GI disorders questionnaire.

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=7 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group n=18 Participants Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group n=3 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Successful Participants With Functional Gallbladder Disorder	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 12 months

Population: Surgical participants with at least 50% improvement in the baseline GERD-HRQL score at 12 months.

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=18 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Successful Surgery Participants With Dissection of Distal Esophagus to Obtain at Least 2.5cm of Tension-free, Intra-abdominal Esophagus Performed.	18 Participants	—	—

SECONDARY outcome

Timeframe: 12 months

Population: Surgical participants with at least 50% improvement in the baseline GERD-HRQL score at 12 months.

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=18 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Successful Surgery Participants With Complete Mobilization of the Fundus, to Include All Short Gastric and Posterior Gastric Vessels to the Base of the Left Crus Performed.	18 Participants	—	—

SECONDARY outcome

Timeframe: 12 months

Population: Surgical participants with at least 50% improvement in the baseline GERD-HRQL score at 12 months.

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=18 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Successful Surgery Participants With Closure of the Crura With Non-absorbable Suture to be Snug With a Dilator of at Least 56 French Diameter Performed.	14 Participants	—	—

SECONDARY outcome

Timeframe: 12 months

Population: Surgical participants with at least 50% improvement in the baseline GERD-HRQL score at 12 months.

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=18 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Successful Surgery Participants With Passage of an Esophageal Dilator of at Least 56 French Diameter Performed.	14 Participants	—	—

SECONDARY outcome

Timeframe: 12 months

Population: Surgical participants with at least 50% improvement in the baseline GERD-HRQL score at 12 months.

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=18 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Successful Surgery Participants With Fundoplication Between 1.5 and 2.5cm in Length Performed.	18 Participants	—	—

SECONDARY outcome

Timeframe: 12 months

Population: Surgical participants with at least 50% improvement in the baseline GERD-HRQL score at 12 months.

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=18 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Successful Surgery Participants With Fundoplication Placed Above the Epiphrenic Fat Pad, Using 3 Sutures Performed.	18 Participants	—	—

SECONDARY outcome

Timeframe: 12 months

Population: Surgical participants with at least 50% improvement in the baseline GERD-HRQL score at 12 months.

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=18 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Successful Surgery Participants With Fundoplication Secured to Esophagus With at Least Two Sutures Performed.	18 Participants	—	—

SECONDARY outcome

Timeframe: 12 months

Population: Surgical participants with at least 50% improvement in the baseline GERD-HRQL score at 12 months.

Outcome measures

Outcome measures
Measure	Medical Treatment Group n=18 Participants baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.	Surgical Treatment Group Nissen fundoplication: laparoscopic antireflux surgery	Placebo Medical Treatment Group baclofen: Baclofen will be prescribed in a dose of 5 mg three times a day (TID) with meals. The dose of baclofen will be increased by 5 mg TID every week until a total dose of 20 mg TID has been achieved. Desipramine: Dose of 25 mg at bedtime (HS) for 1 week, then 50 mg HS for 1 week, then 100 mg HS until the next quarterly visit.
Number of Successful Surgery Participants With Fundoplication Floppiness Demonstrated by Passing a Grasper Between Fundoplication and Dilator-filled Esophagus Performed.	15 Participants	—	—

Adverse Events

Medical Treatment Group

Serious events: 4 serious events

Other events: 18 other events

Deaths: 0 deaths

Surgical Treatment Group

Serious events: 4 serious events

Other events: 17 other events

Deaths: 0 deaths

Placebo Medical Treatment Group

Serious events: 3 serious events

Other events: 18 other events

Deaths: 0 deaths

All Enrolled

Serious events: 15 serious events

Other events: 79 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Stuart Spechler

Dallas VA Medical Center

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place