HIV
Conditions
Keywords
HIV, diarrhea
Brief summary
The purpose of the study is to see if ImmunoLin® will reduce the frequency of bowel movements and gastrointestinal (GI) symptoms in HIV volunteers with persistent GI symptoms. The study will also examine the effect of ImmunoLin® on the bacteria in the gut and the immune system in gut tissue as well as in the blood.
Interventions
DIETARY_SUPPLEMENTImmunolin®
Immunolin® 500 mg capsules to be taken 5 capsules twice daily for eight weeks
Sponsors
Proliant Health & Biologicals
University of California, Davis
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* GI complaints consisting of at least 2 loose or watery stools per day or marked abdominal bloating that adversely effects activities of daily living (ADLs) or common social functioning for greater than 6 months, even though the symptomatology may wax and wane over that time period. * Subjects should have had routine testing to exclude enteric pathogens. * Subjects should have made an effort to identify food intolerance, especially lactose intolerance. * Symptoms should be believed to be independent of ART or other medications known to have the potential to cause similar GI complaints; either because the symptoms predate initiation of the medications or shifts between different options for ART has had no appreciable effect on symptoms. * Over the previous 6 months, alcohol use should be characterized as occasional with less than 1.5 ounces per day being the maximum estimated use (\<2 beers or glasses of wine or 1 drink of hard liquor). * Subjects will be greater than 18 years of age. * Plasma HIV load should be suppressed to less than 400 cp/mL for at least four months, but there is no restriction on peripheral CD4+ T-cell count. Blips of \<1000 cp/mL are allowed, provided that these are not associated with medication interruptions and that the pVL is undetectable before and after the observed blip. * Subjects are willing to maintain a food and GI-symptom diary while receiving the ImmunoLin® supplement. * Subjects should be willing to attempt to maintain a stable regimen of ART for the duration of the study unless indicated for patient safety. * Subjects should be free of antibiotic use for at least 3-weeks prior to study entry except for chronic antibiotics used for prophylaxis according to SOC in HIV management. Usage of antibiotics during the course of the study will be assessed on a case by case basis by the study team. * Subjects must be free of conditions which require chronic therapy that are known to alter the gut flora. Steroid use must be limited to intermittent topical preparations only which includes inhaled or dermatologic routes of application.
Exclusion criteria
* known unrelated causes for GI abnormalities. * abnormal coagulation parameters (PT\>1.2 ULN) * thrombocytopenia (platelet count \<50,000 within 6 weeks) * contra-indications to upper endoscopy or conscious sedation * anemia (\> grade 1 \[appendix D\]) * aspirin, ibuprofen, warfarin or other agents that interfere with the coagulation cascade are prohibited within 1 week of endoscopy. * positive pregnancy test
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Bowel Movements Per Day | 8 weeks (56 days) | self-reported bowel movement in diary |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Pro-inflammatory Bacterial Orders | 8 weeks | 16S rDNA sequencing for Bacteroidetes/Firmicutes ratio |
| Measures of Gut Permeability | 8 weeks | five-hour disaccharide absorption test |
| Systemic Immune Activation | 8 weeks | CD8+ T-cells with an activated phenotype (HLA-DR/CD38+ coexpression) |
| Duodenal Immune Reconstitution | 8 weeks | changes in duodenal lamina propria CD3+/CD4+ density by immunohistochemistry |
Countries
United States
Participant flow
Recruitment details
Patients with diagnosis of HIV enteropathy are eligible for enrollment.
Participants by arm
| Arm | Count |
|---|---|
| ImmunoLin® 8-week treatment course | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | ImmunoLin® |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Age, Continuous | 44.5 years STANDARD_DEVIATION 4.5 |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
Number of Bowel Movements Per Day
self-reported bowel movement in diary
Time frame: 8 weeks (56 days)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| ImmunoLin® | Number of Bowel Movements Per Day | baseline stool frequency | 5.8 bowel movements/day |
| ImmunoLin® | Number of Bowel Movements Per Day | week-8 stool frequency | 2 bowel movements/day |
Comparison: Wilcoxin-rank test used to determine decrease in bowel movements/day after 8 weeks of interventionp-value: 0.008Wilcoxon (Mann-Whitney)
Secondary
Duodenal Immune Reconstitution
changes in duodenal lamina propria CD3+/CD4+ density by immunohistochemistry
Time frame: 8 weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| ImmunoLin® | Duodenal Immune Reconstitution | baseline duodenal CD3+/CD4+ cells | 213 CD3+/CD4+ per mm^2 lamina propria |
| ImmunoLin® | Duodenal Immune Reconstitution | 8 week duodenal CD3+/CD4+ cells | 322 CD3+/CD4+ per mm^2 lamina propria |
p-value: 0.016Wilcoxon (Mann-Whitney)
Secondary
Frequency of Pro-inflammatory Bacterial Orders
16S rDNA sequencing for Bacteroidetes/Firmicutes ratio
Time frame: 8 weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| ImmunoLin® | Frequency of Pro-inflammatory Bacterial Orders | baseline Bacteroidetes/Firmicutes ratio | 0.27 ratio of Bacteroidetes/Firmicutes % |
| ImmunoLin® | Frequency of Pro-inflammatory Bacterial Orders | week-8 Bacteroidetes/Firmicutes ratio | 0.55 ratio of Bacteroidetes/Firmicutes % |
p-value: 0.11Wilcoxon (Mann-Whitney)
Secondary
Measures of Gut Permeability
five-hour disaccharide absorption test
Time frame: 8 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| ImmunoLin® | Measures of Gut Permeability | baseline permiability ratio | .024 percentage absorption |
| ImmunoLin® | Measures of Gut Permeability | week-8 permeability ratio | 0.032 percentage absorption |
p-value: >0.05Wilcoxon (Mann-Whitney)
Secondary
Systemic Immune Activation
CD8+ T-cells with an activated phenotype (HLA-DR/CD38+ coexpression)
Time frame: 8 weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| ImmunoLin® | Systemic Immune Activation | baseline CD8+ activation | 20.1 % CD8/HLA-DR/CD38+ |
| ImmunoLin® | Systemic Immune Activation | week-8 CD8+ activation | 20.3 % CD8/HLA-DR/CD38+ |