Skip to main content
OpenTrials
Completed

NCT Number: NCT04805944

Gut Microbiota, PGx and INSTIs Response

This is an interventional phase IV trial enrolling HIV-infected patients treated by dolutegravir or bictegravir-based combined antiretroviral therapy, and patients with a planned shift to a dolutegravir or bictegravir-based combined antiretroviral therapy, that aims at understanding the individual response to dolutegravir and bictegravir, in terms of efficacy and toxicity.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

HIV Infections Acquired Immunodeficiency Syndrome Blood-Borne Infections Communicable Diseases Genital Diseases Immune System Diseases Immunologic Deficiency Syndromes Infections Lentivirus Infections RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Slow Virus Diseases Urogenital Diseases Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Cliniques universitaires Saint-Luc

Brussels, Belgium

About this study

The main objective of our research project is to better define the inter-individual variability in terms of clinical and biological response towards Integrase Strand Transfer Inhibitors, an important ARV drug class used in the treatment of HIV infection. We aim at identifying predictors of drug efficacy and toxicity, which are eagerly awaited by clinicians as INSTIs are now prescribed worldwide and concerns about previously unidentified side effects are emerging.

The specific objectives of the project are:

  • To study the impact of genetic polymorphisms in selected pharmacogenes (including genes coding for biotransformation enzymes and transport proteins) on INSTIs PK parameters and biomarkers relevant for TDM, such as trough (C0) and intracellular (IC) concentrations.
  • To determine whether genetic polymorphisms in selected pharmacogenes might affect INSTIs efficacy, as assessed by the measurement of the viral load.
  • To address the important question of the pathophysiological mechanisms lying behind the two main side effects of INSTIs, namely neuropsychiatric adverse events and abnormal weight gain.
  • To describe how INSTIs affect the gut microbiome of treated patients, and to determine in turn how and by which pathways the gut microbiome might influence the clinical response (i.e. efficacy and toxicity) to INSTIs.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion will be proposed to:

  • HIV infected adult patient regularly followed at Centre de reference HIV of CUSL and currently treated by 50mg OD of DTG (n=80) or 50mg OD of BIC (n=30).
  • Virally controlled immunologically functional HIV infected adult patient regularly followed at Centre de reference HIV of CUSL and shifting from another ARV class to a treatment containing 50mg OD of DTG (n=20) or 50mg OD of BIC (n=20).
  • HIV infected adult patient retrospectively identified as having stopped standard dosage of DTG (ie. 50mg OD) due to NPAE (insomnia, depression, anxiety) (n=50). Identification will be based on the interrogation of our prospective clinical database.

Exclusion criteria

  • Pregnancy at the time of inclusion or expected pregnancy within 12 months, for patients treated by DTG or BIC during the study
  • Liver failure (Child-Pugh A, B or C)

Treatment and study plan

Dolutegravir

Drug

Dolutegravir treated patients will be included and samples (blood for pharmacokinetic, pharmacogenetic et metabolite profiling, stools for microbiota profiling) drawn at follow-up.

Bictegravir

Drug

Bictegravir treated patients will be included and samples (blood for pharmacokinetic, pharmacogenetic and metabolite profiling, stools for microbiota profiling) drawn at follow-up.

Primary outcomes

  1. Dolutegravir and bictegravir through concentration

    Time frame: 24 hours post last dose

    Measurement of drug through concentration for groups A, B, D and E

  2. Dolutegravir and bictegravir intracellular concentration

    Time frame: 24 hours post last dose

    Measurement of drug intracellular concentration for groups A, B, D and E

  3. Viral replication

    Time frame: At least 3 months after the initiation of DTG/BIC

    Viral replication measured for groups A, B, D and E

  4. Microbiota profile under treatment

    Time frame: At least 6 months after the initiation of DTG/BIC

    Determination microbiota profile for groups A, B, C, D and E

  5. Change of microbiota profile

    Time frame: Baseline and at 6 months

    Change from baseline microbiota profile at 6 month after treatment initiation, for groups D and E

  6. Change in weight

    Time frame: Through study completion, an average of 1 year

    Overall weight change between treatment initiation through study completion

  7. Psychometric evaluation (Symptom-checklist-90-R)

    Time frame: At least 3 months after the initiation of DTG/BIC

    Psychometric evaluation through Symptom-checklist-90-R questionnaire, for groups A and B.

    The mean scores of each of the 10 subscales of Symptom-checklist-90-R will be calculated. A global severity index is computed as the average score of all 90 items. A higher score indicates a worse outcome.

  8. Change of psychometric evaluation (Symptom-checklist-90-R)

    Time frame: Baseline and at 6 months

    Change from baseline Symptom-checklist-90-R at 6 month after treatment initiation, for groups D and E.

    The mean scores of each of the 10 subscales of Symptom-checklist-90-R will be calculated. A global severity index is computed as the average score of all 90 items. A higher score indicates a worse outcome.

  9. Psychometric evaluation (Pittsburgh Sleep Quality Index)

    Time frame: At least 3 months after the initiation of DTG/BIC

    Psychometric evaluation through Pittsburgh Sleep Quality Index questionnaire, for groups A and B.

    Pittsburgh Sleep Quality Index scores answers from 0 to 21. A higher score means a worse outcome.

  10. Change of psychometric evaluation (Pittsburgh Sleep Quality Index)

    Time frame: Baseline and at 6 months

    Change from baseline Pittsburgh Sleep Quality Index at 6 month after treatment initiation, for groups D and E.

    Pittsburgh Sleep Quality Index scores answers from 0 to 21. A higher score means a worse outcome.

  11. Psychometric evaluation (Pichot's fatigue scale)

    Time frame: At least 3 months after the initiation of DTG/BIC

    Psychometric evaluation through Pichot's fatigue scale questionnaire, for groups A and B.

    Pichot's fatigue scale scores answers between 0 and 32. A higher score means a worse outcome.

  12. Change of psychometric evaluation (Pichot's fatigue scale)

    Time frame: Baseline and at 6 months

    Change from baseline Pichot's fatigue scale at 6 month after treatment initiation, for groups D and E.

    Pichot's fatigue scale scores answers between 0 and 32. A higher score means a worse outcome.

  13. Psychometric evaluation (Hospital Anxiety and Depression Scale)

    Time frame: At least 3 months after the initiation of DTG/BIC

    Psychometric evaluation through Hospital Anxiety and Depression Scale questionnaire, for groups A and B.

    Hospital Anxiety and Depression Scale scores answers between 0 and 21 for its two compoinents, anxiety and depression. A higher score means a worse outcome.

  14. Change of psychometric evaluation (Hospital Anxiety and Depression Scale)

    Time frame: Baseline and at 6 months

    Change from baseline Hospital Anxiety and Depression Scale at 6 month after treatment initiation, for groups D and E.

    Hospital Anxiety and Depression Scale scores answers between 0 and 21 for its two compoinents, anxiety and depression. A higher score means a worse outcome.

Sponsors and collaborators

Lead sponsor

Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Other

Registry information

Official study title

Gut Microbiota, Pharmacogenetics and Integrase Strand Transfer Inhibitors Response

Important dates

Study start
2021
Primary completion
2023
Study completion
2023
First posted
Mar 18, 2021
Registry last updated
May 10, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.