HIV-1-infection on Healthy VolunteersPhase 1DTG ClampNCT04771754

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

A Phase 1 study testing Dolutegravir in people with HIV-1-infection on Healthy Volunteers, run by Chelsea and Westminster NHS Foundation Trust at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 18 to 60 yearsHealthy volunteers can take part
Conditions the study is for: HIV-1-infection on Healthy Volunteers
What is being tested?: Dolutegravir
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 16 participants
Where: 1 siteUnited Kingdom
Study dates: 20 Mar 2022to 10 Jan 2024
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 60 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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

Show all 47Show fewer

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)*;
Any other method with published data showing that the expected failure rate is <1% per year
Men who have partners who are women of childbearing potential (WOCBP - definition in Appendix 6) must be using an adequate method of contraception to avoid pregnancy in their partner throughout the study and for a period of at least 4 weeks after the study;
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 patient;
Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide);
Any intrauterine device (IUD) with published data showing that the expected failure rate is <1% per year (not all IUDs meet this criterion, see Appendix 4 for an example listing of approved IUDs) plus male condom;
Sterilisation confirmed prior to the subject's entry into the study
Approved hormonal contraception used by female partner (see protocol appendix 4 for a listing of examples of approved hormonal contraception) plus male condom;
Any other method with published data showing that the expected failure rate is <1% per year and not containing hormones plus male condom.
Any contraception method must be used consistently, in accordance with the approved product label and for at least four weeks after discontinuation of IMP (Appendix 6).
Any contraception method must be used consistently, in accordance with the approved product label and for at least 28 days prior to the first dose of study medication and 4 weeks after discontinuing the study medication.
4.1.2 Exclusion Criteria
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
Thiazide diuretics and indapamide
Thyroid preparations
Psychotropic agents
Anabolic steroids
Megestrol acetate
Dofetilide (or pilsicainide)

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

Arnold Xhikola
London, SW10 0XD

Other trials in United Kingdom

About this study

Read the detailed description

A randomised, crossover study investigating the difference in changes in insulin sensitivity (determined by peripheral glucose uptake using a euglycaemic clamp) with the administration of dolutegravir (DTG) compared to no DTG for 28 days in HIV seronegative healthy volunteers.

Participants will be randomised 1:1 to one of two arms:

Group 1:

Dolutegravir 50 mg once daily for the first 28 days of the study.
No treatment for the last 44 days of the study.

Group 2:

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

Research bloods, endocrine profiles, weight and urine samples will be collected at baseline, as well as day 28, 44, and 72 to enable comparative analyses.

Participants will be closely monitored whilst taking the study medications. Participants will exit the study 72 days post-randomisation, with a follow-up call 28 days after exiting.

Conditions: HIV-1-infection on Healthy Volunteers
Being tested: Dolutegravir
Keywords: HIV, Dolutegravir, Insulin
Medical subject headings: Insulin Resistance

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

DolutegravirDrug
Also called Tivicay
50 mg once daily orally

Study groups in NCT04771754
Study group	Role	What they receive
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. Receives: 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). Receives: Drug: Dolutegravir

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline, day 28 and 72 for both groups.

Secondary outcomes (12)

Effect of Dolutegravir on Adipocytokines.
Fasting adiponectin levels in blood.
Measured: Baseline, day 28 and 72 for both groups.
Effect of Dolutegravir on Pituitary Hormones
Cortisol
Measured: Baseline, day 28 and 72 for both groups.
Effect of Dolutegravir on Changes in Indirect Calorimetry
Indirect calorimetry by ventilated hood expires gas analysis will be used to determine energy expenditure during the course of the clamp procedures.
Measured: Baseline, day 28 and 72 for both groups.
Effect of Dolutegravir on Adipocytokines.
Fasting Leptin levels in blood.
Measured: Baseline, day 28 & 72 for both groups.
Effect of Dolutegravir on Adipocytokines.
Fasting Ghrelin levels in blood.
Measured: Baseline, day 28 & 72 for both groups.
Effect of Dolutegravir on Pituitary Hormones
Prolactin
Measured: Baseline, day 28 and 72 for both groups.
Effect of Dolutegravir on Pituitary Hormones
Luteinsing Hormone Level
Measured: Baseline, day 28 and 72 for both groups.
Effect of Dolutegravir on Pituitary Hormones
Growth Hormone
Measured: Baseline, day 28 and 72 for both groups.
Effect of Dolutegravir on Lipid Profile Including Lipid Fractions
Total Cholesterol
Measured: Baseline, day 28 and 72 for both groups.
Effect of Dolutegravir on Lipid Profile Including Lipid Fractions
Triglycerides
Measured: Baseline, day 28 and 72 for both groups.
Changes in Food Intake by Food Preference Questionnaire
Changes in food intake Food preference questionnaire for adolescents and adults (FPQ)
1- Scoring of Individual Items
Each food item is rated on a 5-point Likert scale:
1. = Dislike a lot
2. = Dislike a little
3. = Neither like nor dislike
4. = Like a little
5. = Like a lot
Responses marked as "Not applicable" are treated as missing and not included in scoring.
Food Category Scores
Items are grouped into six categories, each scored by averaging across the foods in that group:
Vegetables (18 items)
Fruits (7 items)
Meat/Fish (12 items)
Dairy (10 items)
Snacks (9 items)
Starches (6 items)
The category score is the mean of item scores in that category (sum ÷ number of items).
For both individual items and category scores:
Minimum possible score = 1 ("Dislike a lot") Maximum possible score = 5 ("Like a lot")
Direction of Scoring On the FPQ, higher scores reflect greater liking of the foods, Lower scores indicate less liking.
'scores on a scale'
Measured: Baseline, day 28 and 72 for both groups.
Change in Sleep Parameters by Sleep Questionnaires
changes in sleep parameters by Pittsbrough Sleep Quality Index (PSQI)
1. Scoring Components The PSQI has 19 self-rated items, grouped into 7 component scores: Subjective sleep quality Sleep latency Sleep duration Habitual sleep efficiency Sleep disturbances Use of sleeping medication Daytime dysfunction Each component is scored from 0 to 3, where higher values indicate worse sleep in that domain.
2. Global Score
The 7 component scores are summed to yield a global PSQI score ranging from 0 to 21.
0 = no difficulty / very good sleep quality
21 = severe difficulties / very poor sleep quality
3- Interpretation
A global score > 5 is commonly used as a cut-off to distinguish between "good sleepers" (≤5) and "poor sleepers" (>5).
4- Direction of Scoring
On the PSQI, higher scores indicate worse outcomes (poorer sleep quality).
Lower scores indicate better sleep quality.
Unit of Measue = Score on a scale
Measured: Baseline, day 28 and 72 for both groups.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

20 Mar 202210 Jan 2024

First posted25 Feb 2021
Study start20 Mar 2022
Primary completion31 Dec 2023
Study completion10 Jan 2024

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for HIV-1-infection on Healthy VolunteersStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Model description: 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).
Masking: None (open label)
Enrolment: 16 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04771754
Sponsor's protocol ID: CRF003
Acronym: DTG Clamp
Status last verified: Nov 2025
First submitted: 20 Jan 2021
Last updated: 2 Dec 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Study at a glance

From the registry record, last updated by the sponsor on 2 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The Effect of Dolutegravir on Whole-body Insulin Sensitivity, Lipid and Endocrine Profile in Healthy Volunteers
ClinicalTrials.gov ID: NCT04771754
Acronym / sponsor ID: DTG Clamp / CRF003
Conditions: HIV-1-infection on Healthy Volunteers
Keywords: HIV, Dolutegravir, Insulin
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 16 participants (actual)
Lead sponsor: Chelsea and Westminster NHS Foundation TrustUniversity, hospital or other
Study start: 20 Mar 2022 (actual)
Primary completion: 31 Dec 2023 (actual)
Study completion: 10 Jan 2024 (actual)
First posted: 25 Feb 2021 (actual)
Results: Posted 2 Dec 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Participants will be randomised 1:1 to one of two arms:

Group 1:

Dolutegravir 50 mg once daily for the first 28 days of the study.
No treatment for the last 44 days of the study.

Group 2:

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

Research bloods, endocrine profiles, weight and urine samples will be collected at baseline, as well as day 28, 44, and 72 to enable comparative analyses.

Participants will be closely monitored whilst taking the study medications. Participants will exit the study 72 days post-randomisation, with a follow-up call 28 days after exiting.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2
Model description: 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).

Arm	Type	Receives
Arm 1	Experimental	Drug: Dolutegravir* 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.
Arm 2	Experimental	Drug: Dolutegravir* 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).

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (47 listed)

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)

Key exclusion criteria (0 listed)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
DolutegravirAlso: Tivicay50 mg once daily orally	Drug	Arm 1, Arm 2

Primary outcome

Change in Insulin Sensitivity in Participants From Baseline to End of Study Between Two Crossover Groups.
Time frame: Baseline, day 28 and 72 for both groups.
Change in insulin sensitivity will be determined by peripheral glucose uptake using a euglycaemic clamp.

12 secondary outcomes

Effect of Dolutegravir on Adipocytokines.
Time frame: Baseline, day 28 and 72 for both groups.
Effect of Dolutegravir on Pituitary Hormones
Time frame: Baseline, day 28 and 72 for both groups.
Effect of Dolutegravir on Changes in Indirect Calorimetry
Time frame: Baseline, day 28 and 72 for both groups.
Effect of Dolutegravir on Adipocytokines.
Time frame: Baseline, day 28 & 72 for both groups.
Effect of Dolutegravir on Adipocytokines.
Time frame: Baseline, day 28 & 72 for both groups.
Effect of Dolutegravir on Pituitary Hormones
Time frame: Baseline, day 28 and 72 for both groups.
Effect of Dolutegravir on Pituitary Hormones
Time frame: Baseline, day 28 and 72 for both groups.
Effect of Dolutegravir on Pituitary Hormones
Time frame: Baseline, day 28 and 72 for both groups.
Effect of Dolutegravir on Lipid Profile Including Lipid Fractions
Time frame: Baseline, day 28 and 72 for both groups.
Effect of Dolutegravir on Lipid Profile Including Lipid Fractions
Time frame: Baseline, day 28 and 72 for both groups.
Changes in Food Intake by Food Preference Questionnaire
Time frame: Baseline, day 28 and 72 for both groups.
Change in Sleep Parameters by Sleep Questionnaires
Time frame: Baseline, day 28 and 72 for both groups.

Results and safety

Results posted to the registry on 2 Dec 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Arm 1	8	7
Arm 2	8	8

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

Time frame: Baseline, day 28 and 72 for both groups.. Mean (Standard Deviation). Unit: (mg/kg/min)

Measure	Arm 1 n = 7	Arm 2 n = 8
Baseline	7.749985 (3.520332)	6.286017 (2.072026)
Day 28	8.716221 (2.600469)	6.815305 (2.404083)
Day 72	10.62598 (5.250227)	7.684051 (2.516086)

Population analysed: Dolutegravir versus No Treatment Two sample Wilcoxon rank sum (Mann Whitney) test

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: total 100 days for both interventions. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Arm 1 Dolutegravir	0 of 7 (0%)	7 of 7 (100%)	0 of 7
Arm 1 No treatment	0 of 7 (0%)	7 of 7 (100%)	0 of 7
Arm 2 No treatment	1 of 8 (12.5%)	8 of 8 (100%)	0 of 8
Arm 2 Dolutegravir	0 of 8 (0%)	8 of 8 (100%)	0 of 8

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Ruth Bryne principal investigator

Chelsea and Westminster Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Dolutegravir in people with HIV-1-infection on Healthy Volunteers, run by Chelsea and Westminster NHS Foundation Trust at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 47 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Insulin Sensitivity in Participants From Baseline to End of Study Between Two Crossover Groups. (time frame: Baseline, day 28 and 72 for both groups.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04771754.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2025.