Gut Microbiota, PGx and INSTIs Response

HIV Infections Clinical Trial

Official title:

Gut Microbiota, Pharmacogenetics and Integrase Strand Transfer Inhibitors Response

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04805944
• Other study ID #: INSTI
• Status: Completed
• Start date: March 10, 2021
• Est. completion date: December 31, 2023

Study information

• Verified date: May 2024
• Source: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 180
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Dolutegravir
Dolutegravir treated patients will be included and samples (blood for pharmacokinetic, pharmacogenetic et metabolite profiling, stools for microbiota profiling) drawn at follow-up.
• Bictegravir
Bictegravir treated patients will be included and samples (blood for pharmacokinetic, pharmacogenetic and metabolite profiling, stools for microbiota profiling) drawn at follow-up.
• Dolutegravir
Patient having discontinued dolutegravir will be included and samples (blood for pharmacogenetic and metabolite profiling, stools for microbiota profiling) drawn at follow-up.
• Dolutegravir
Patients starting dolutegravir will be included and sampled both before (blood for pharmacogenetic and metabolite profiling, stools for microbiota profiling) and after (blood for pharmacokinetic and metabolite profiling, stools for microbiota profiling) the start of dolutegravir
• Bictegravir
Patients starting bictegravir will be included and sampled both before (blood for pharmacogenetic and metabolite profiling, stools for microbiota profiling) and after (blood for pharmacokinetic and metabolite profiling, stools for microbiota profiling) the start of bictegravir

Locations

Country	Name	City	State
Belgium	Cliniques universitaires Saint-Luc	Brussels

Sponsors (1)

Lead Sponsor	Collaborator
Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dolutegravir and bictegravir through concentration	Measurement of drug through concentration for groups A, B, D and E	24 hours post last dose
Primary	Dolutegravir and bictegravir intracellular concentration	Measurement of drug intracellular concentration for groups A, B, D and E	24 hours post last dose
Primary	Viral replication	Viral replication measured for groups A, B, D and E	At least 3 months after the initiation of DTG/BIC
Primary	Microbiota profile under treatment	Determination microbiota profile for groups A, B, C, D and E	At least 6 months after the initiation of DTG/BIC
Primary	Change of microbiota profile	Change from baseline microbiota profile at 6 month after treatment initiation, for groups D and E	Baseline and at 6 months
Primary	Change in weight	Overall weight change between treatment initiation through study completion	Through study completion, an average of 1 year
Primary	Psychometric evaluation (Symptom-checklist-90-R)	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.	At least 3 months after the initiation of DTG/BIC
Primary	Change of psychometric evaluation (Symptom-checklist-90-R)	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.	Baseline and at 6 months
Primary	Psychometric evaluation (Pittsburgh Sleep Quality Index)	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.	At least 3 months after the initiation of DTG/BIC
Primary	Change of psychometric evaluation (Pittsburgh Sleep Quality Index)	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.	Baseline and at 6 months
Primary	Psychometric evaluation (Pichot's fatigue scale)	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.	At least 3 months after the initiation of DTG/BIC
Primary	Change of psychometric evaluation (Pichot's fatigue scale)	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.	Baseline and at 6 months
Primary	Psychometric evaluation (Hospital Anxiety and Depression Scale)	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.	At least 3 months after the initiation of DTG/BIC
Primary	Change of psychometric evaluation (Hospital Anxiety and Depression Scale)	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.	Baseline and at 6 months