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: THE RAGTIME STUDY

NCT03029689 | Completed Phase 3 Results

• 1 other identifier: RAGTIME
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

The project presented here will be the first prospective, randomized evaluation of the effect of ART on the structure and function of the gut microbiome. This study provides a unique opportunity to understand the benefits of ART with high intestinal penetration on the gut microbiome. It is thus a key study to understand the bidirectional interactions between the microbiome and the host in people living with HIV/AIDS.

Conditions

HIV

Keywords

HIV infection; Gut microbiome; Raltegravir; Raltegravir intensification; Bacterial richness

Outcome Measures

Primary Outcomes (1)

• Bacterial Gene Richness (Observed Unique Genes). Analysis of the Composition, Structure and Function of the Intestinal Microbiome. *

  -\* Structure and composition of the microbiome. DNA will be extracted and purified from fecal samples and cryopreserved at -80ºC until amplification. The purified DNA will be amplified using Illumina-tagged primers to amplify the V3 and V4 16S ribosomal DNA (rDNA) regions. PCR reactions will be performed in triplicate to preserve diversity. Pooled triplicates will be sequenced ensuring adequate sampling depth. -Function of the bacteriome. The gene content will be inferred from the abundance of each bacteria in the intestinal bacteriome according to the 16S rDNA information

  From baseline to 48 weeks

Secondary Outcomes (8)

• Association of the Gut Microbiome With Inflammation Markers

  From baseline to week 48

• Association of the Gut Microbiome With Coagulation

  From baseline to 48 weeks

• Association of the Gut Microbiome With Enterocyte Damage

  From baseline to 48 weeks

• Association of the Gut Microbiome With Bacterial Translocation and Monocyte Activation

  From baseline to 48 weeks

• Mean Fluorescence Intensity (MFI) Measure of Maturation, Activation, Exhaustion and Immune Senescence Markers in CD4+ and CD8+ T-cells

  Differences at week 48

Study Arms (2)

Current ART + Raltegravir

EXPERIMENTAL

Current ART + Raltegravir

Drug: Raltegravir; Drug: Current ART

Current ART + placebo

PLACEBO COMPARATOR

Current ART + placebo

Drug: Placebo; Drug: Current ART

Interventions

Raltegravir DRUG

Raltegravir 1200 mg (2 tablets x 600mg) once daily plus current ART during 48 weeks from randomization

Also known as: NP

Current ART + Raltegravir

Placebo DRUG

Placebo (2 tablets of placebo) once daily plus current ART during 48 weeks from randomization.

Also known as: NP

Current ART + placebo

Current ART DRUG

3-drug antiretroviral treatment including PI/r/c or NNRTI

Also known as: NP

Current ART + Raltegravir; Current ART + placebo

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years old
• Documented HIV infection
• Stable 3-drug antiretroviral treatment including PI/r/c or NNRTI for at least 6 months.
• Plasma HIV-1 RNA load \<50 copies/mL for at least 12 months.
• Signed Informed Consent

You may not qualify if:

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

Sponsors & Collaborators

• Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Germans Trias i Pujol Hospital

Badalona, Barcelona, 08916, Spain

Location

MeSH Terms

Conditions

HIV Infections

Interventions

Raltegravir Potassium

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Roger Paredes
• Organization: Fundació Lluita Contra les Infeccions

rparedes@lluita.org

(+34) 93 465 7897

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2017
• First Posted: January 24, 2017
• Study Start: July 28, 2017
• Primary Completion: April 30, 2020
• Study Completion: April 30, 2020
• Last Updated: June 17, 2025
• Results First Posted: April 13, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)