The Effect of Dolutegravir on Whole-body Insulin Sensitivity, Lipid and Endocrine Profile in Healthy Volunteers

NCT04771754 | Completed Phase 1 Results

• 1 other identifier: CRF003
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This study will investigate changes in insulin resistance, lipid metabolism and endocrine profile in HIV-negative subjects exposed to dolutegravir (an antiretroviral drug used in HIV treatment) in order to investigate the role all these different factors may potentially have in weight gain recently reported in clinical cohorts.

Conditions

HIV-1-infection on Healthy Volunteers

Keywords

HIV; Dolutegravir; Insulin

Outcome Measures

Primary Outcomes (1)

• Change in Insulin Sensitivity in Participants From Baseline to End of Study Between Two Crossover Groups.

  Change in insulin sensitivity will be determined by peripheral glucose uptake using a euglycaemic clamp.

  Baseline, day 28 and 72 for both groups.

Secondary Outcomes (12)

• Effect of Dolutegravir on Adipocytokines.

  Baseline, day 28 and 72 for both groups.

• Effect of Dolutegravir on Pituitary Hormones

  Baseline, day 28 and 72 for both groups.

• Effect of Dolutegravir on Changes in Indirect Calorimetry

  Baseline, day 28 and 72 for both groups.

• Effect of Dolutegravir on Adipocytokines.

  Baseline, day 28 & 72 for both groups.

• Effect of Dolutegravir on Adipocytokines.

  Baseline, day 28 & 72 for both groups.

Study Arms (2)

Arm 1

EXPERIMENTAL

* Dolutegravir - 50 mg once daily, orally administered for the first 28 days of the study. * No treatment for the last 44 days of the study.

Drug: Dolutegravir

Arm 2

EXPERIMENTAL

* No treatment for the first 28 days of the study. * Dolutegravir - 50 mg once daily, orally administered for the last 28 days of the study (day 44-72).

Drug: Dolutegravir

Interventions

Dolutegravir DRUG

50 mg once daily orally

Also known as: Tivicay

Arm 1; Arm 2

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Willing and able to provide informed consent
• Cis-Male and Cis-Female healthy subjects without underlying conditions
• Subjects must have documented negative HIV serology by ELISA and P24 antigen and not receiving anti-HIV pre-exposure prophylaxis (PreP)
• Subjects must be clinically well volunteers aged between 18 to 60 years with BMI \<30 kg/m2 but \>18 kg/m2
• Healthy, as determined by the investigator or medically qualified designee based on a medical evaluation, including medical history, physical examination, laboratory tests, and cardiac evaluation (including ECG)
• Non-fasting blood glucose, total cholesterol and triglycerides within normal limits
• Subjects should have complete blood count (FBC) with normal differential and platelet count (detail below of specified normal range, table 1)
• Table 1 - Compete FBC with normal differential \& platelets count ranges Test Male Normal Range Female Normal Range Haemoglobin (g/L) 130-168 114-150 White blood cell count (x109/L) 4.2-10.6 4.2-11.2 Neutrophil count (x109/L) 2.0 - 7.1 Lymphocyte count (x109/L) 1.1 - 3.6 Monocyte count (x109/L) 0.2 - 0.9 Eosinophil count (x109/L) 0.0 - 0.5 Basophil count (x109/L) 0.0 - 0.2
• A female, may be eligible to enter and participate in the study if she:
• is of non-child-bearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy or,
• is of child-bearing potential with a negative pregnancy test at both Screening and Day 1 and agrees to use one of the following methods of contraception to avoid pregnancy:
• Complete abstinence from penile-vaginal intercourse. Abstinence is acceptable only as true abstinence when this is in line with the preferred and usual lifestyle of the participant;
• Any intrauterine device with published data showing that the expected failure rate is \<1% per year (not all intrauterine devices meet this criterion, see Appendix 6\] for an example listing of approved intrauterine devices);
• Male partner sterilization confirmed prior to the female subject's entry into the study, and this male is the sole partner for that subject;
• Approved hormonal contraception (see Appendix 6\] for a listing of examples of approved hormonal contraception)\*;

You may not qualify if:

• Subjects with a waist hip ratio \> 0.97 or BMI \> 30kg/m2 and BMI \<18 kg/m2 will be excluded
• Acute or chronic hepatitis B infection (determined by positive hepatitis B surface antigen result at the screening visit)
• Acute or chronic hepatitis C infection (determined by positive hepatitis C antibody result at the screening visit)
• Diabetes mellitus, other metabolic syndrome or disease process in the opinion of the investigator likely to cause marked disturbance in glucose and lipid homeostasis including hypertension. Subject with HbA1c \>42 mmol/mol will be excluded.
• History or presence of allergy to the dolutegravir
• ALT or AST greater than or equal to 1.5 x Upper Limit of Normal (ULN) and total bilirubin greater than or equal to 1.5 x ULN excluded;
• Pregnancy and breastfeeding women
• Alcohol consumption \>10 units/week
• Clinically relevant drug use (positive urine drug screen) or history of alcohol or drug use considered by the Investigator to be sufficient to hinder compliance with treatment, follow-up procedures or evaluation of adverse events. Smoking is permitted, but tobacco intake should remain consistent throughout the study.
• Unable to refrain from the use of prescription (e.g., dofetilide) or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives prior to the baseline visit and throughout the study until the follow-up period, unless in the opinion of the Investigator the medication will not interfere with the study procedures or compromise participant safety.
• This includes on-going therapy with any of the following
• Metabolically active medications
• Any lipid-lowering medication
• Any testosterones treatments or supplements - Glucocorticoids including inhaled steroids except for 'as necessary' use
• Beta-blockers

Sponsors & Collaborators

• Chelsea and Westminster NHS Foundation Trust: lead

Study Sites (1)

Arnold Xhikola

London, SW10 0XD, United Kingdom

Location

MeSH Terms

Conditions

Insulin Resistance

Interventions

dolutegravir

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Dr Ruth Byrne
• Organization: Chelsea and Westminster Hospital NHS Foundation Trust

ruthbyrne@nhs.net

02033152560

Study Officials

• Ruth Bryne

  Chelsea and Westminster Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Subjects will be randomised to start on dolutegravir 50 mg once daily OR no treatment for the first 28 day dosing phase of the study then will cross over to the alternative for the second dosing phase, following a 2 week washout period (equivalent to 5+ dolutegravir elimination half-lives).

Study Record Dates

• First Submitted: January 20, 2021
• First Posted: February 25, 2021
• Study Start: March 20, 2022
• Primary Completion: December 31, 2023
• Study Completion: January 10, 2024
• Last Updated: December 2, 2025
• Results First Posted: December 2, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)