Clinical trial to evaluate the effect of Raltegravir intensification (1.200 mg QD) on the gut microbiota of chronically HIV-1 infected subject over time

Phase 1

• Conditions: HIV-1; MedDRA version: 19.0Level: LLTClassification code 10068341Term: HIV-1 infectionSystem Organ Class: 100000004862; Therapeutic area: Diseases [C] - Virus Diseases [C02]

• Registration Number: EUCTR2016-002722-36-ES
• Lead Sponsor: FUNDACIÓ LLUITA CONTRA LA SIDA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-01-04
• Last Update Posted: 3 April 2017

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Age =18 years old
2. Documented HIV infection
3. Stable antiretroviral treatment including PIi/r or NNRTIi-based 3 drugs ART for at least 6 months.
4. Plasma HIV-1 RNA load <50 copies/mL for at least 12 months.
5. Signed Informed Consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. PI/r monoterapy
2. INSTI therapy during the previous 6 months
3. Evidence of previous INSTI resistance
4. Creatine clearance <50 mL/min
5. Child- Pugh B or C
6. History of active uncontrolled GI disorders or diseases including:
6.1. Major surgery of the GI tract, with the exception of cholecystectomy and appendectomy, in the previous 5 years.
6.2. Any major bowel resection at any time
6.3. Any chronic digestive disease such as peptic ulcer, Crohn’s disease, ulcerative colitis, coeliac disease, confirmed intolerance to lactose or indeterminate colitis.
6.4. Persistent infectious gastroenteritis, colitis or gastritis; persistent or chronic diarrhea of unknown etiology; Clostridium difficile infection (recurrent) or Helicobacter pylori infection (untreated);
6.5. Irritable bowel syndrome (moderate-severe)
6.6. Chronic constipation
6.7. Active proctitis
7. Antibiotic therapy within the previous 2 months
8. In women, pregnancy or breastfeeding

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the ability of raltegravir intensification to increase gut microbiome richness and modify the gut microbiome composition of people living with HIV receiving stable ART.;Secondary Objective: To correlate changes in the gut microbiota composition and richness with markers of inflammation, coagulation, enterocyte damage, bacterial translocation and T-cell maturation, activation, exhaustion and senescence during raltegravir intensification.;Primary end point(s): Increase in bacterial richness (observed species).;Timepoint(s) of evaluation of this end point: At week 48, relative to baseline (week 0).

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): •Longitudinal changes in:<br>-Gut bacterial composition <br>-Gut bacterial function<br>-Other estimators of richness and diversity: Chao1, ACE, Shannon, 1/Simpson. <br>•Association of the gut microbiome composition and richness with:<br>-Inflammation: IL-6, IP-10<br>-Coagulation: D-Dimer<br>-Enterocyte damage: Intestinal Fatty Acid Binding Protein (I-FABP)<br>-Bacterial translocation and monocyte activation: LPS-binding protein (LBP), soluble CD14. <br>-Maturation, activation, exhaustion and immune senescence in CD4+ and CD8+ T-cells: CD3+, CD4+, CD8+, CD45RA, CCR7, CD28, CD27, HLA-DR, CD38, PD-1, CD57. <br>-CD4 and CD8+ counts <br>-CD4+/CD8+ ratio;Timepoint(s) of evaluation of this end point: Baseline, weeks 12, 24, 48