Trial Outcomes & Findings for Gastrointestinal Sensorimotor Dysfunctions in Diabetes Mellitus (NCT NCT02170870)

Results Overview

Intestinal chemosensitivity was recorded by evaluating symptoms during duodenal lipid infusion (0.5 gm/mL diluted in water to 222 mL) and placebo or the glucagon like peptide 1 (GLP-1) receptor antagonist exendin 9-39 over 2 hours. Participants reported the severity of 6 symptoms (nausea, fullness, bloating, abdominal pain, belching, and burning) at 15 minute intervals using a Visual Analogue Scale (VAS) marked 0 (minimum value) - 4 (maximum value): absent (0), light (1), moderate (2), severe (3) and intolerable(4). The scores recorded for nausea, fullness, bloating, and abdominal pain over the 2 hour infusion were averaged and reported as the mean symptom score. Higher scores mean a worse outcome.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

104 participants

Primary outcome timeframe

Day 1, approximately 2 hours after infusion

Results posted on

2019-04-23

Participant Flow

Subjects were recruited from Mayo Clinic in Rochester, Minnesota.

Participant milestones

Participant milestones
Measure	Healthy Controls Exendin 9-39 Exendin 9-39 was administered intravenously (1,200 pmol/kg bolus followed by infusion at 300 pmol/kg/min). Lipid infusion 66.7 mL Microlipid (0.5 gm/mL diluted in water to 222 ml).	Healthy Controls Placebo Normal saline infusion was prepared to match the appearance of Exendin 9-39. Lipid infusion 66.7 mL Microlipid (0.5 gm/mL diluted in water to 222 ml)	Diabetics Exendin 9-39 Exendin 9-39 was administered intravenously (1,200 pmol/kg bolus followed by infusion at 300 pmol/kg/min). Lipid infusion 66.7 mL Microlipid (0.5 gm/mL diluted in water to 222 ml)	Diabetics Placebo Normal saline infusion was prepared to match the appearance of Exendin 9-39. Lipid infusion 66.7 mL Microlipid (0.5 gm/mL diluted in water to 222 ml).	Functional Dyspepsia Exendin 9-39 Exendin 9-39 was administered intravenously (1,200 pmol/kg bolus followed by infusion at 300 pmol/kg/min). Lipid infusion 66.7 mL Microlipid (0.5 gm/mL diluted in water to 222 ml).	Functional Dyspepsia Placebo Normal saline infusion was prepared to match the appearance of Exendin 9-39. Lipid infusion 66.7 mL Microlipid (0.5 gm/mL diluted in water to 222 ml).
Overall Study STARTED	13	11	20	20	20	20
Overall Study COMPLETED	13	11	20	20	20	20
Overall Study NOT COMPLETED	0	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Healthy Controls Exendin 9-39 n=13 Participants Exendin 9-39 was administered intravenously (1,200 pmol/kg bolus followed by infusion at 300 pmol/kg/min). Lipid infusion 66.7 mL Microlipid (0.5 gm/mL diluted in water to 222 ml).	Healthy Controls Placebo n=11 Participants Normal saline infusion was prepared to match the appearance of Exendin 9-39. Lipid infusion 66.7 mL Microlipid (0.5 gm/mL diluted in water to 222 ml).	Diabetics Exendin 9-39 n=20 Participants Exendin 9-39 was administered intravenously (1,200 pmol/kg bolus followed by infusion at 300 pmol/kg/min). Lipid infusion 66.7 mL Microlipid (0.5 gm/mL diluted in water to 222 ml).	Diabetics Placebo n=20 Participants Normal saline infusion was prepared to match the appearance of Exendin 9-39. Lipid infusion 66.7 mL Microlipid (0.5 gm/mL diluted in water to 222 ml).	Functional Dyspepsia Exendin 9-39 n=20 Participants Exendin 9-39 was administered intravenously (1,200 pmol/kg bolus followed by infusion at 300 pmol/kg/min). Lipid infusion 66.7 mL Microlipid (0.5 gm/mL diluted in water to 222 ml).	Functional Dyspepsia Placebo n=20 Participants Normal saline infusion was prepared to match the appearance of Exendin 9-39. Lipid infusion 66.7 mL Microlipid (0.5 gm/mL diluted in water to 222 ml).	Total n=104 Participants Total of all reporting groups
Age, Continuous	36 years STANDARD_DEVIATION 12.6 • n=13 Participants	42 years STANDARD_DEVIATION 14.3 • n=11 Participants	45 years STANDARD_DEVIATION 15.7 • n=20 Participants	45 years STANDARD_DEVIATION 11.6 • n=20 Participants	44 years STANDARD_DEVIATION 13.2 • n=20 Participants	39 years STANDARD_DEVIATION 13 • n=20 Participants	42.3 years STANDARD_DEVIATION 13 • n=104 Participants
Sex: Female, Male Female	8 Participants n=13 Participants	6 Participants n=11 Participants	16 Participants n=20 Participants	15 Participants n=20 Participants	15 Participants n=20 Participants	16 Participants n=20 Participants	76 Participants n=104 Participants
Sex: Female, Male Male	5 Participants n=13 Participants	5 Participants n=11 Participants	4 Participants n=20 Participants	5 Participants n=20 Participants	5 Participants n=20 Participants	4 Participants n=20 Participants	28 Participants n=104 Participants
Race and Ethnicity Not Collected	—	—	—	—	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment United States	13 participants n=13 Participants	11 participants n=11 Participants	20 participants n=20 Participants	20 participants n=20 Participants	20 participants n=20 Participants	20 participants n=20 Participants	104 participants n=104 Participants
BMI	26 kg/m2 STANDARD_DEVIATION 4.4 • n=13 Participants	26 kg/m2 STANDARD_DEVIATION 5.3 • n=11 Participants	29 kg/m2 STANDARD_DEVIATION 6.6 • n=20 Participants	27 kg/m2 STANDARD_DEVIATION 4.5 • n=20 Participants	26 kg/m2 STANDARD_DEVIATION 6.4 • n=20 Participants	27 kg/m2 STANDARD_DEVIATION 6.9 • n=20 Participants	26.8 kg/m2 STANDARD_DEVIATION 5.2 • n=104 Participants

PRIMARY outcome

Timeframe: Day 1, approximately 2 hours after infusion

Population: Functional Dyspepsia arm - enteral lipid infusion was not performed because a nasoduodenal tube could not be placed in 2 functional dyspepsia placebo subjects and 3 functional dyspepsia exendin 9-39 subjects.

Intestinal chemosensitivity was recorded by evaluating symptoms during duodenal lipid infusion (0.5 gm/mL diluted in water to 222 mL) and placebo or the glucagon like peptide 1 (GLP-1) receptor antagonist exendin 9-39 over 2 hours. Participants reported the severity of 6 symptoms (nausea, fullness, bloating, abdominal pain, belching, and burning) at 15 minute intervals using a Visual Analogue Scale (VAS) marked 0 (minimum value) - 4 (maximum value): absent (0), light (1), moderate (2), severe (3) and intolerable(4). The scores recorded for nausea, fullness, bloating, and abdominal pain over the 2 hour infusion were averaged and reported as the mean symptom score. Higher scores mean a worse outcome.

Outcome measures

Outcome measures
Measure	Healthy Controls Exendin 9-39 n=13 Participants Exendin 9-39 was administered intravenously (1,200 pmol/kg bolus followed by infusion at 300 pmol/kg/min). Lipid infusion 66.7 mL Microlipid (0.5 gm/mL diluted in water to 222 ml).	Healthy Controls Placebo n=11 Participants Normal saline infusion was prepared to match the appearance of Exendin 9-39. Lipid infusion 66.7 mL Microlipid (0.5 gm/mL diluted in water to 222 ml). Microlipid: Lipid infusion {66.7 mL Microlipid (0.5 gm/mL diluted in water to 222 ml).	Diabetics Exendin 9-39 n=20 Participants Exendin 9-39 was administered intravenously (1,200 pmol/kg bolus followed by infusion at 300 pmol/kg/min). Lipid infusion 66.7 mL Microlipid (0.5 gm/mL diluted in water to 222 ml).	Diabetics Placebo n=20 Participants Normal saline infusion was prepared to match the appearance of Exendin 9-39. Lipid infusion 66.7 mL Microlipid (0.5 gm/mL diluted in water to 222 ml). Microlipid: Lipid infusion {66.7 mL Microlipid (0.5 gm/mL diluted in water to 222 ml).	Functional Dyspepsia Exendin 9-39 n=17 Participants Exendin 9-39 was administered intravenously (1,200 pmol/kg bolus followed by infusion at 300 pmol/kg/min). Lipid infusion 66.7 mL Microlipid (0.5 gm/mL diluted in water to 222 ml).	Functional Dyspepsia Placebo n=18 Participants Normal saline infusion was prepared to match the appearance of Exendin 9-39. Lipid infusion 66.7 mL Microlipid (0.5 gm/mL diluted in water to 222 ml).
Mean Intestinal Chemosensitivity to Lipids Perfusion	0.22 score on a scale Standard Deviation 0.05	0.36 score on a scale Standard Deviation 0.13	0.55 score on a scale Standard Deviation 0.11	0.65 score on a scale Standard Deviation 0.17	1.4 score on a scale Standard Deviation 0.9	1.2 score on a scale Standard Deviation 0.9

SECONDARY outcome

Timeframe: Day 1

The time for half of the ingested solids or liquids to leave the stomach. Following a meal consisting of two eggs labeled with technetium Tc 99m sulfur colloid (1 mCi) served on one slice of bread with milk labeled with indium In111 diethylenetriaminepentaacetate (0.1 mCi), gastric emptying of solids and liquids was assessed with scintigraphy. Rapid emptying is defined as ≥ 36% emptied at one hour and delayed emptying is defined as \< 76% emptied at four hours. Normal emptying is defined as amount less than rapid emptying definition but greater than delayed emptying definition.