Clinical Trial to Evaluate the Addition to an Antiretroviral Treatment of a Probiotic

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate a therapy for the inflammaging (premature aging).

Detailed Description
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It's been demonstrated that the HIV-1 virus is associated to the reduction of the microbiota. Some studies suggest that because of this bacterial reduction, the premature aging appears. So this study aims to demonstrate that our probiotic can balance the microbiota as a preventive solution for the inflammaging.

Official Title
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Clinical Trial, Randomized and Controlled With Placebo to Evaluate the Addition to an Antiretroviral Treatment of a Probiotic, Only or in Conjunction of a Pre-biotical, in Adults Infected by Hiv-1 With a cd4 Record Less Than 500 Cells / mm3

Conditions
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HIV, Premature Aging

Intervention / Treatment
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* Dietary Supplement: Probiotic
* Dietary Supplement: Prebiotic
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Older than 18 years old. Documented HIV-1 infection. Be in treatment with these antiretrovirals (INI, IP, ITINAN) during 12 months. HIV-1 Viral titer <50 copies/mL during 6 months. CD4> 500 cells/mm3. Exclusion Criteria: Treatment with antibiotics. Severe diseases actives. Defining diseases of AIDS in the previous year. Gut surgery except appendectomy or cholecystectomy. Pregnancy. Any diet deviation (vegans). Other probiotic treatment.

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 100 patients will be included in this trial. Patients will be randomized 2: 2: 1 to one of the following 3 branches according to the use of integrase inhibitors (INI), protease inhibitors (PI) or non-nucleoside analogue reverse transcriptase inhibitors ( ITINAN) and according to the CD4 count nadir is greater or less or equal to 200 cells / mm3: Branch A: add probiotic i3.1 to the antiretroviral therapy Branch B: add probiotic i3.1 and ProSeed prebiotic to the antiretroviral therapy Branch C: add placebo to ART The treatment periods will be of 6 months and follow-up will be carried out at month, at 3 months and at 6 after the start of the study treatment, and a last visit will be made at 3 months after discontinuing it (wash-out period).
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: i3.1<br>This group will have their habitual antiretroviral therapy (integrase inhibitor (INI), protease inhibitor (IP), reverse transcriptase inhibitor (ITINAN)) combined with the research product (probiotic i3.1). The prebiotic will be taken once a day during 6 months. | Dietary Supplement: Probiotic<br>* The probiotic i3.1 is a commercialized product. It will be supplied by the promoter and manufactured in ALIFARM S.A. It contains: Lactobacillus plantarum CECT7484 Lactobacillus plantarum CECT7485 Pediococcus acidilactici CECT7483<br>|
| Experimental: i3.1 + ProSeed<br>This group will have their habitual antiretroviral therapy combined with the probiotic (i3.1) and the prebiotic (ProSheed). The prebiotic and probiotic will be taken once a day during 6 months. | Dietary Supplement: Probiotic<br>* The probiotic i3.1 is a commercialized product. It will be supplied by the promoter and manufactured in ALIFARM S.A. It contains: Lactobacillus plantarum CECT7484 Lactobacillus plantarum CECT7485 Pediococcus acidilactici CECT7483<br>Dietary Supplement: Prebiotic<br>* ProSeed prebiotic is a non-commercialized product. It will be supplied by the promoter and manufactured in ALIFARM S.A. It contains: Partially Hydrolyzed Guar Gum (PHGG) Inulin HPD Oat Beta-Glucans Pectin Inulin Low Protein Diet (LPD) Polydextrose Maltrodextrins<br>|
| Placebo Comparator: Placebo<br>This group will only have their habitual antiretroviral therapy. The placebo will be taken once a day during 6 months. | Dietary Supplement: Placebo<br>* It is a non-commercialized product. It is composed of the same excipients as the probiotic and the prebiotic. It will be supplied by the promoter and manufactured in ALIFARM S.A.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The appearance of adverse effects. | Percentage of patients with adverse events (AE) in the 3 study arms: i3.1, i3.1 + ProSeed and Placebo. | Change from Baseline Adverse Effects will be measured at 1 month and 3 months after the treatment beginning (V1 and V2 respectively). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gut microbiota diversity and metabolomic profile | Biodiversity changes among the basal visit and 3 months after (in each arm), measured using the Shannon Index. | A measure will be made in V1, V2, V3 and V4 (1 month, 3 months, 6 months and 9 months after the treatment beginning, respectively). | 
| Translocational bacterial markers & Systemic inflammation markers | Markers changes among the basal visit and 3 months after, in each arm.The plasma levels of lipopolysaccharide, sCD14, Interleukin 6 and Iinterleukin 10 will be measured. | A measure will be made in V1 and V2 (1 month and 3 months after the treatment beginning, respectively). | 
| Cluster of Differentation 4 (CD4) count | Recount changes (cells/mm3) among the basal visit and 3 months after, in each arm. | A measure will be made in V2, V3 and V4 (3 months, 6 months and 9 months after the treatment beginning, respectively). | 
| CD4/CD8 ratio | Ratio changes among the basal visit and 3 months after, in each arm. | A measure will be made in V2, V3 and V4 (3 months, 6 months and 9 months after the treatment beginning, respectively). | 
| Satisfaction with the product | This parameter will be measured in order to evaluate the satisfaction of the patient with the research product. The satisfaction with the product wil be measured with the Likert Scale (with answers from satisfied to unsatisfied). | A measure will be made in V2, V3 and V4 (3 months, 6 months and 9 months after the treatment beginning, respectively). | 
| Questionaire to evaluate the life quality | This parameter will be measured with the Medical Outcomes Study-HIV questionaire (with answers from not affected to affected). | A measure will be made in V2, V3 and V4 (3 months, 6 months and 9 months after the treatment beginning, respectively). | 
| Questionaires to evaluate the anxiety and depression | This parameter will be measured with the Hospital Anxiety Depression Scale (HADS) questionaire (with answers from never to always). | A measure will be made in V2, V3 and V4 (3 months, 6 months and 9 months after the treatment beginning, respectively). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-1