Trial Outcomes & Findings for Autonomic Neuropathy, GI Motility, and Inflammation in HIV (NCT NCT02850276)

NCT ID: NCT02850276

Last Updated: 2019-05-29

Results Overview

Breath Test at week 8 as compared to baseline. Breath test results is the rise in the combined hydrogen and methane during the breath test.

• Recruitment status: COMPLETED
• Study phase: EARLY_PHASE1
• Target enrollment: 76 participants
• Primary outcome timeframe: baseline and week 8
• Results posted on: 2019-05-29

Participant Flow

Enrollment period from November 2015 to Jan 2018

Participant milestones

Measure	Pyridostigmine 30mg PO three times a day for 8 weeks
Overall Study STARTED	76
Overall Study COMPLETED	15
Overall Study NOT COMPLETED	61

Reasons for withdrawal

Measure	Pyridostigmine 30mg PO three times a day for 8 weeks
Overall Study screen failure	43
Overall Study Withdrawal by Subject	14
Overall Study Physician Decision	2
Overall Study Lost to Follow-up	2

Baseline Characteristics

Autonomic Neuropathy, GI Motility, and Inflammation in HIV

Baseline characteristics by cohort

Measure	Pyridostigmine n=76 Participants 30mg PO three times a day for 8 weeks
Age, Continuous	56.9 years STANDARD_DEVIATION 6.6 • n=5 Participants
Sex: Female, Male Female	20 Participants n=5 Participants
Sex: Female, Male Male	56 Participants n=5 Participants
Race/Ethnicity, Customized African-American	39 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic/Latino	22 Participants n=5 Participants
Race/Ethnicity, Customized White	14 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants
Current CD4+ count	602 cells/mm^3 n=5 Participants
Nadir CD4+ count	200 cells/mm^3 n=5 Participants
Duration of know HIV infection	21 years n=5 Participants
Early Satiety GI symptom	43 Participants n=5 Participants
Post-prandial bloating GI symptom	55 Participants n=5 Participants
Nausea	53 Participants n=5 Participants
Post-prandial vomiting	15 Participants n=5 Participants
Cramping/colicky abdominal pain	41 Participants n=5 Participants
Moderate to severe diarrhea	30 Participants n=5 Participants
Moderate to severe constipation	31 Participants n=5 Participants
Vagal sub-score >=1	30 Participants n=5 Participants
Adrenal sub-score >=1	55 Participants n=5 Participants
Sudomotor sub-score >=1	63 Participants n=5 Participants
Total CASS >=3	49 Participants n=5 Participants
Autonomic neuropathy CASS vagal subscore >=1	30 Participants n=5 Participants
Autonomic neuropathy BRS-V of <4	33 Participants n=5 Participants
Autonomic neuropathy CASS >=3	49 Participants n=5 Participants

PRIMARY outcome

Timeframe: baseline and week 8

Breath Test at week 8 as compared to baseline. Breath test results is the rise in the combined hydrogen and methane during the breath test.

Outcome measures

Measure	Pyridostigmine n=15 Participants 30mg PO three times a day for 8 weeks
Change in Breath Test Baseline	28 ppm Interval 14.0 to 50.0
Change in Breath Test week 8	14 ppm Interval 9.0 to 31.0

PRIMARY outcome

Timeframe: week 8

Number of participants with reduction in Small intestinal bacterial overgrowth (SIBO) assessed with breath testing after 8 weeks of treatment.

The hydrogen breath test for the detection of small intestinal bacterial overgrowth (SIBO), obtained by having participants exhale into a plastic bag. the hydrogen content of the samples is measured using a commercially available analyzer.

Outcome measures

Measure	Pyridostigmine n=15 Participants 30mg PO three times a day for 8 weeks
Number of Participants With Reduction in Small Intestinal Bacterial Overgrowth (SIBO)	13 Participants

SECONDARY outcome

Timeframe: Baseline and week 8

Percent retention of gastric contents on gastric emptying study. GI dysmotility calculated from gastric emptying scintigraphy - measurement of the percent retention of gastric contents at 4 hours.

Outcome measures

Measure	Pyridostigmine n=15 Participants 30mg PO three times a day for 8 weeks
Mean Percent Retention of Gastric Contents on Gastric Emptying Study Baseline	3 percent retention of gastric contents Interval 2.0 to 4.0
Mean Percent Retention of Gastric Contents on Gastric Emptying Study week 8	2 percent retention of gastric contents Interval 2.0 to 4.0

SECONDARY outcome

Timeframe: Baseline and week 8

Change in sCD14 level at week 8 as compared to baseline. sCD14 is a marker of macrophage activation commonly used as an indirect measure of translocation

Outcome measures

Measure	Pyridostigmine n=15 Participants 30mg PO three times a day for 8 weeks
Change in sCD14 Level Baseline	2573 mean florescence intensity Interval 1859.0 to 3063.0
Change in sCD14 Level Week 8	2095 mean florescence intensity Interval 1784.0 to 2584.0

SECONDARY outcome

Timeframe: Baseline and week 8

TNFα is a pro-inflammatory cytokine which is induced by components of translocating bacteria. Change in TNFα level at week 8 compared to baseline

Outcome measures

Measure	Pyridostigmine n=15 Participants 30mg PO three times a day for 8 weeks
Change in TNFα Level Baseline	134.0 mean florescence intensity Interval 114.0 to 152.0
Change in TNFα Level week 8	117.5 mean florescence intensity Interval 108.0 to 136.0

SECONDARY outcome

Timeframe: Baseline and week 8

Change in IL-6 plasma level at week 8 as compared to baseline. Plasma interleukin-6 (IL-6), an important inflammatory mediator which predicts mortality in HIV as well as multiple medical co-morbidities, presumably via inflammatory mechanisms.

Outcome measures

Measure	Pyridostigmine n=15 Participants 30mg PO three times a day for 8 weeks
Change in IL-6 Plasma Level Baseline	30.5 mean florescence intensity Interval 25.0 to 36.0
Change in IL-6 Plasma Level Week 8	26.5 mean florescence intensity Interval 23.0 to 39.0

SECONDARY outcome

Timeframe: Baseline and week 8

The gastrointestinal domain domain score of the COMPASS contains 12 items which reflect gastrointestinal symptoms of autonomic function. It is scored on a total scale of 0-28, with higher numbers reflecting worse symptoms.

Outcome measures

Measure	Pyridostigmine n=15 Participants 30mg PO three times a day for 8 weeks
The Composite Autonomic Symptom Score (COMPASS) Baseline	8 score on a scale Standard Deviation 4
The Composite Autonomic Symptom Score (COMPASS) Week 8	8.6 score on a scale Standard Deviation 4.8

SECONDARY outcome

Timeframe: Baseline and week 8

Medical Outcomes Study (MOS-HIV) quality of life questionnaire. It is a 35 item questionnaire covering 11 dimensions of health including physical functioning, role functioning, pain, social functioning, emotional well-being, energy/fatigue, cognitive functioning, general health, health distress, overall QOL, and health transition. The total scale ranges from 0-100 with a higher score representing better functioning and well-being.

Outcome measures

Measure	Pyridostigmine n=15 Participants 30mg PO three times a day for 8 weeks
Medical Outcomes Study Questionnaire Baseline	66.1 score on a scale Standard Deviation 6.2
Medical Outcomes Study Questionnaire Week 8	65 score on a scale Standard Deviation 7

Adverse Events

Pyridostigmine

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Pyridostigmine n=15 participants at risk 30mg PO three times a day for 8 weeks
Gastrointestinal disorders Stomach Cramps	6.7% 1/15 • 8 weeks
Gastrointestinal disorders Diarrhea	20.0% 3/15 • 8 weeks
Gastrointestinal disorders Flatulence	6.7% 1/15 • 8 weeks
General disorders Dizziness	6.7% 1/15 • 8 weeks

Additional Information

Dr. Jessica Robinson-Papp

Icahn School of Medicine at Mount Sinai

Phone: 212-241-8390

Email: jessica.robinson-papp@mssm.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place