Status:
COMPLETED
The Effect of Dolutegravir on Whole-body Insulin Sensitivity, Lipid and Endocrine Profile in Healthy Volunteers
Lead Sponsor:
Chelsea and Westminster NHS Foundation Trust
Conditions:
HIV-1-infection on Healthy Volunteers
Eligibility:
All Genders
18-60 years
Phase:
PHASE1
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 ord...
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...
Eligibility Criteria
Inclusion
- Inclusion Criteria
- 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)\*;
- 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.
- 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)
Exclusion
Key Trial Info
Start Date :
March 20 2022
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
January 10 2024
Estimated Enrollment :
16 Patients enrolled
Trial Details
Trial ID
NCT04771754
Start Date
March 20 2022
End Date
January 10 2024
Last Update
December 2 2025
Active Locations (1)
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1
Arnold Xhikola
London, United Kingdom, SW10 0XD