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

June 6, 2025 updated by: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia

Randomized, Double-blind, Placebo-controlled 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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The gut microbiome is essential for the maturation of the neonatal immune system and the adequate development and function of adult immune responses. HIV-1 infection in children and adults exerts a rapid and severe depletion of gut-associated lymphoid tissue, which damages the intestinal barrier, allowing translocation of gut commensal bacteria into the systemic circulation. Bacterial translocation causes chronic inflammation and immune activation, which lead to immune deterioration and premature aging of HIV-1-infected subjects, including metabolic disturbances, cardiovascular diseases, cognitive disorders and HIV-associated cancers. Persistence of residual HIV-1 replication in the presence of ART has been associated to incomplete HIV-1 suppression in gut lymphatic tissues due to suboptimal tissular penetration of PI/s or NNRTIs.

In previous work in our institute, the investigators have observed that HIV-1 infection is independently associated with significant reductions in the gut microbiome richness, which is, in turn, are inversely correlated with systemic inflammation. Reduced microbial richness, for example, has been associated with intestinal inflammatory diseases and well as with metabolic syndrome, diabetes and obesity and correlated with metabolic markers.

Recovering bacterial richness might thus have a positive impact on immune activation, chronic inflammation and the overall health of HIV-infected individuals. However, achieving that goal will possibly require, alongside potential bacterial supplementations, the use of ART with high penetration into gut lymphoid tissue to limit as much as possible the continued damage exerted by residual HIV replication on the GALT. Antiretroviral drugs with higher intestinal penetration like raltegravir may be more effective at recovering the intestinal microbiome composition and function than those with lower gut penetration like darunavir or the NNRTIs. Thereby, raltegravir intensification could be associated with increases in intestinal microbial richness, implying an improvement on intestinal and overall health.

Despite the lack of evidence on that regard, previous studies from our group and others would favor that hypothesis. Residual HIV-1 replication in plasma can be deterred by ART intensification with raltegravir, which is, in part, due to the high penetration of raltegravir in intestinal tissues. Moreover, raltegravir intensification decreases peripheral CD8 T-cell activation CD45RA (-) and creates a transient CD4 T-cell redistribution, which revert after raltegravir withdrawal.

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

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
61

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
    • Barcelona
      • Badalona, Barcelona, Spain, 08916
        • Germans Trias i Pujol Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 99 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

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

Exclusion Criteria:

  1. PI/r monotherapy
  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*.

    • Female subjects of childbearing potential must not be pregnant, not be planning a pregnancy or breast-feeding. Sexually active women must be willing to use two approved methods of contraception (including condoms, diaphragm, spermicides, hormonal methods and/or intrauterine devices) from baseline until the end of the clinical trial. Sexually active men in heterosexual relationships must be willing to use two approved method of contraception with their partners from baseline until the end of the clinical trial.
    • condom use is considered as an additional method of contraception only and cannot be the only method of contraception used as not been considered an effective method by the Clinical Trial Facilitation Group (CTFG) guidelines.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Current ART + Raltegravir
Drug: Raltegravir
Raltegravir 1200 mg (2 tablets x 600mg) once daily plus current ART during 48 weeks from randomization
Other Names:
  • NP
Drug: Current ART
3-drug antiretroviral treatment including PI/r/c or NNRTI
Other Names:
  • NP
Placebo Comparator: Current ART + placebo
Drug: Current ART
3-drug antiretroviral treatment including PI/r/c or NNRTI
Other Names:
  • NP
Drug: Placebo
Placebo (2 tablets of placebo) once daily plus current ART during 48 weeks from randomization.
Other Names:
  • NP

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Bacterial Gene Richness (Observed Unique Genes). Analysis of the Composition, Structure and Function of the Intestinal Microbiome. *
Time Frame: From baseline to 48 weeks

-* 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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Association of the Gut Microbiome With Inflammation Markers
Time Frame: From baseline to week 48
IL-6, IP-10
From baseline to week 48
Association of the Gut Microbiome With Coagulation
Time Frame: From baseline to 48 weeks
D-Dimer
From baseline to 48 weeks
Association of the Gut Microbiome With Enterocyte Damage
Time Frame: From baseline to 48 weeks
Intestinal Fatty Acid Binding Protein (I-FABP)
From baseline to 48 weeks
Association of the Gut Microbiome With Bacterial Translocation and Monocyte Activation
Time Frame: From baseline to 48 weeks
LPS-binding protein (LBP), soluble CD14
From baseline to 48 weeks
Mean Fluorescence Intensity (MFI) Measure of Maturation, Activation, Exhaustion and Immune Senescence Markers in CD4+ and CD8+ T-cells
Time Frame: Differences at week 48
CCR7, CD28, CD27, HLA-DR, CD38, PD-1, CD57
Differences at week 48
Association of the Gut Microbiome Composition and Richness With CD4 and CD8+ Counts.
Time Frame: Baseline
CD4 and CD8+ counts
Baseline
Other Estimators of Richness and Diversity
Time Frame: From baseline to 48 weeks
Shannon
From baseline to 48 weeks
Association of the Gut Microbiome Composition and Richness With CD4/CD8+ Cell Ratio.
Time Frame: Baseline
CD4/CD8+ cell ratio
Baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Merck Sharp & Dohme LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 28, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 30, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 30, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 11, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 20, 2017

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 24, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 17, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 6, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RAGTIME

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on HIV

Clinical Trials on Raltegravir

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings