Camu Camu in ART-treated People Living With HIV

Study Overview
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Brief Summary
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Persons living with HIV and receiving antiretroviral therapy (ART) remain with inflammation leading to higher risks of cardiovascular diseases, fatty liver and cancer. It has been observed in colitis and in HIV infection that abnormal composition of the gut microbes and leaky gut induce inflammation contributing to diabetes, fatty liver and cardiovascular risks. Abundance of Akkermansia muciniphila in stool, a type of good bacteria acting as a shield on the gut barrier has been shown to prevent obesity, diabetes and to improve cancer treatment response. Health food (prebiotic) increases the frequency of A. muciniphila in overweight individuals. Dr Marette, a study collaborator from Laval University, has recently published (Gut, 2018) that an extract from a Brazilian fruit called Camu Camu (CC) protects mice from obesity, reduce LPS, a marker for passage of microbes from the gut into the blood and decreases inflammation in association with the frequency of A. muciniphila in stools. The extract of CC is sold in nutritional stores to regulate body fat. The investigators will invite 22 participants to take 2 capsules of CC daily for 12 weeks in addition to their ART. CC tolerance and changes in blood and stools for inflammation and microbe composition will be evalutated at the end of the 12-week treatment and 8 weeks post-intake. An optional sub study will assess the changes of gut barrier by doing biopsies by colonoscopy. CC is expected to beassociated with an enrichment of A. muciniphila in stools, combined with reduced gut damage and inflammation.

Official Title
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FULL TITLE: Camu Camu Effects on Circulating LPS and Systemic Immune Activation in ART-treated Participants: The Camu Camu Pilot Study

Conditions
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HIV Infections

Intervention / Treatment
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* Biological: Camu Camu Capsules


Participation Criteria
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Eligibility Criteria
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3.2 Inclusion Criteria Participants will be eligible for the study if they meet the following criteria: Male or female adults ≥18 years of age. Documented HIV-1 infection by Western Blot, Enzyme Immuno Assay (EIA) or viral load assay. On any ART for at least 2 years, with viremia less than 50 copies/ml during the last two years (occasional blips allowed). On a stable ART regimen (same prescription) for at least 3 months. CD4 count >200 and a CD4/CD8 ratio <1 suggesting an increase in inflammation and risk for non-AIDS events. Able to communicate adequately in either French or English. Able and willing to provide written informed consent prior to screening. Women of childbearing potential must have a negative serum pregnancy test. Women of childbearing potential must agree to use one of the following approved methods of birth control while in the study and until 2 weeks after completion: Complete abstinence from penile-vaginal intercourse from the screening period until two weeks after the study completion. Double barrier methods (acceptable barrier methods include diaphragm, coil, contraceptive foam, sponge with spermicide, condom); or Oral, injectable or implant contraceptives plus one barrier method; Intrauterine device (IUD) plus one barrier method; or Male partner sterilization confirmed prior to the female participant's entry into the study; this male is the sole partner for that participant. Approved hormonal contraception, started at least 30 days before screening. Another method approved by the trial physician with published data showing that the expected failure rate is <1% per year preferably with condom. Any contraception method must be used consistently, in accordance with the approved product label, and for the duration of the study until two weeks after study completion. Women of non-child-bearing potential as defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥ 45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy. Sexually active men with a female partner of childbearing potential must agree to one of the following methods of birth control: The use at least one barrier method of contraception (e.g. condom) with a female partner using a second approved method of contraception (IUD, hormonal contraceptive pill, diaphragm, spermicide etc.) during the study and until two weeks after study completion. Be confirmed sterile. Have had a successful vasectomy. Exclusion Criteria Participants are not eligible to participate in the study if they meet any of the following conditions: Known allergy/hypersensitivity to Camu Camu. Current AIDS-related event or serious health condition including systemic infections in the last 3 months. Severe systemic diseases (e.g. uncontrolled hypertension, chronic renal failure), or active uncontrolled infections. Co-infection with active Hepatitis B or C Virus. Current use or have used in the past 3 months: immune-modulatory agents/chemotherapeutics, prophylactic antibiotics35/antibiotics, proton pump inhibitors, phosphate binders, Metformin or Morphine as these drugs can interact with vitamin C or modulate gut microbiota. Diagnosis of diabetes mellitus (HbA1c≥6.5%) as defined by the Canadian Clinical Practice Guidelines for the Prevention and Management of Diabetes42. Frequent use of polyphenol-rich prebiotics (e.g. cranberry and CC powders and/or capsules) in the last 12 months. Statin or other anti-cholesterol treatment use in the last 3 months. Recent changes in dietary habits, intermittent fasting, chronic constipation or laxative use as these can affect gut microbiota. Psychiatric or cognitive disturbance or any illness that could preclude compliance with the study. Current participation in an experimental therapy study or receipt of experimental therapy within the last 6 months. Women who are pregnant, planning to become pregnant, or breast-feeding. A score of higher than 8 on a Full AUDIT questionnaire (See Appendix 1) at the screening visit, suggesting an alcohol abuse problem.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Camu Camu<br>Assessments will be done at baseline, during and after 12 weeks of Camu Camu intake. | Biological: Camu Camu Capsules<br>* Camu Camu powder encapsulated (500mg each). 2 capsules per day will be used for this study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of the plasma marker of microbial translocation LPS, assessed using ELISA. |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of CC | measured by evaluating adverse events, hematology, and serum chemistries over the course of the study. These evaluations will include HIV viral load, glucose levels, a lipid profile and plasma levels of hsCRP and D-dimer. | 20 weeks | 
| Changes in gut integrity markers I-FABP, and sST2, measured by ELISA |  | 12 weeks and 20 weeks | 
| Changes in microbial translocation marker 1-3-b-D-Glucan assessed using the Fungitell assay |  | 12 weeks and 20 weeks. | 
| Changes in pro-inflammatory markers (IL-1β, IL-6, IL-8, IL-18. IP-10, IL-17A and F, IL-22, and soluble CD14) and anti-inflammatory markers (IL-10) assessed by ELISA. |  | 12 weeks and 20 weeks | 
| Changes in T-cell and monocyte activation levels assessed by flow cytometry using markers CD38, HLA-DR and PD-1 |  | 12 weeks and 20 weeks | 
| Changes in A. muciniphila levels in stools using qPCR |  | 12 weeks and 20 wekks | 
| Changes in microbiota composition and diversity in stools assessed using 16s rDNA sequencing |  | 12 weeks and 20 wekks | 
| Changes in HIV reservoir size in blood assessed by PCR |  | 12 weeks and 20 wekks | 
| Evaluate intra-patient variability using data from two baseline visits, approximately two weeks apart from each other to confirm reliability of baseline results. |  | 2 weeks | 
| Changes in gut mucosa architecture in a subset of participants who will consent to have colon biopsies before and at the end of the 12 weeks of CC treatment. |  | 12 weeks | 
| Changes in inflammation in gut mucosa biopsy assessed by myeloperoxidase staining before and at the end of the 12 weeks of CC treatment |  | 12 weeks | 
| Changes in HIV reservoir size in biopsies using qPCR |  | 12 weeks | 
| Association between baseline gut microbiota composition (16S rDNA sequencing), and markers of gut integrity (I-FABP, tissue staining) and inflammation (T-cell activation, inflammatory cytokines). |  | 2 weeks |