Contribution of Dolutegravir to Obesity and Cardiovascular Disease

NCT04340388 | Completed Phase 4 FDA Drug

• 1 other identifier: 1553691-1
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of the study is to combine a collaborative and translational approach to evaluate the effect antiretroviral regimen switch to a dolutegravir containing regimen compared to continued treatment with a non- dolutegravir based regimen on on lipid and metabolic profiles, renal function, body composition, vascular function and diet.

Conditions

HIV-1-infection; Antiviral Drug Adverse Reaction; Vascular Diseases; Cardiovascular Abnormalities; Abnormality of Adipose Tissue; Body Weight Changes; Body Fat Disorder; HIV-Associated Lipodystrophy Syndrome

Outcome Measures

Primary Outcomes (1)

• Change in Weight

  Change from baseline kilograms (kg) of weight at 24 weeks

  24 weeks

Secondary Outcomes (3)

• Change in body mass index (BMI)

  24 weeks

• Change in vascular endothelial function

  24 weeks

• Height

  24 weeks

Other Outcomes (7)

• Change in cholesterol

  24 weeks

• Change in triglycerides

  24 weeks

• Change in high density lipoprotein (HDL)

  24 weeks

Study Arms (2)

Switch from a non-integrase based regimen to dolutegravir

ACTIVE COMPARATOR

Participants with HIV-1 infection who have had viral suppression on a non-integrase based antiretroviral regimen for greater than or equal to 3 months will be switched to a dolutegravir based regimen dosed at 50 milligrams (MG) once daily. Background regimen will remain the same.

Drug: Dolutegravir 50 MG

Continue on non-integrase inhibitor based regimen

ACTIVE COMPARATOR

Participants not currently on an integrase based regimen who remain on current suppressive therapy will remain on current antiretroviral regimen.

Drug: Antiretroviral/Anti HIV

Interventions

Dolutegravir 50 MG DRUG

15 participants will be randomized to remain on fully suppressive background antiretroviral therapy. The third agent will be switched to dolutegravir at the dose of 50 mg daily.

Also known as: Tenofovir alafenamide, Tenofovir disoproxil fumarate, Abacavir, Lamivudine, Darunavir, Cobicistat, Rilpivirine, Combivir, Zidovudine

Switch from a non-integrase based regimen to dolutegravir

Antiretroviral/Anti HIV DRUG

15 participants with suppressed HIV disease for greater than or equal to 3 months will be randomized to remain on their current 2 or 3 drug fully suppressive antiretroviral regimen.

Also known as: Antiretroviral Combinations

Continue on non-integrase inhibitor based regimen

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must meet the following criteria to be eligible for participation in this study:
• Age greater than or equal to 18 years with HIV-1 who have been virologically suppressed (HIV-1 RNA \< 50 copies for greater than or equal to 3 months on a non-integrase strand transfer inhibitor-based regimen
• Have the ability to understand and sign an informed consent written in the English language

You may not qualify if:

• Age less than 18 years without HIV-1 infection
• Has hypersensitivity or other contraindication to any of the components of the study
• Has active diagnosis of untreated hepatitis due to any cause
• Has a history or current evidence of any condition, laboratory abnormality or other circumstance ( including drug or alcohol use or dependence) that might confound the results of the study or interfere with the subject's participation for the full duration of the study
• Is taking or is anticipated to require long term systemic immunosuppressive therapy, immune modulators, or any prohibited therapies from 60 days prior to Screening/Day 1 visit through to the end of study
• Has documented or suspected dolutegravir-associated resistance mutations specifically:
• Q148H/K/R/N in combination with E138K or G1402/A or N155H.
• Has a life expectancy less than or equal to one year
• Is pregnant, breastfeeding, or expecting to donate eggs or sperm or conceive or father a child at any time during the study and 6 weeks following the end of study.

Sponsors & Collaborators

• Augusta University: lead

Study Sites (1)

Augusta University

Augusta, Georgia, 30912, United States

Location

Related Publications (1)

• Cottrell ML, Hadzic T, Kashuba AD. Clinical pharmacokinetic, pharmacodynamic and drug-interaction profile of the integrase inhibitor dolutegravir. Clin Pharmacokinet. 2013 Nov;52(11):981-94. doi: 10.1007/s40262-013-0093-2.

  PMID: 23824675 RESULT

MeSH Terms

Conditions

Vascular Diseases; Cardiovascular Abnormalities; Body Weight Changes; HIV-Associated Lipodystrophy Syndrome

Interventions

dolutegravir; tenofovir alafenamide; Tenofovir; abacavir; Lamivudine; Darunavir; Cobicistat; Rilpivirine; lamivudine, zidovudine drug combination; Zidovudine

Condition Hierarchy (Ancestors)

Cardiovascular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Lipodystrophy; Skin Diseases, Metabolic; Skin Diseases; Skin and Connective Tissue Diseases; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides; Sulfonamides; Amides; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Sulfur Compounds; Furans; Thiazoles; Azoles; Nitriles; Thymidine

Study Officials

• Jonell B Poe, MPAS

  Augusta University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Clinical Professor, Physician Assistant

Model Details: The study design is a randomized control trial where patients will be randomized to the dolutegravir or non-dolutegravir arms by random number generation using the statistical software R. A unique identification (ID) key from 1 to 2n will be assigned to each patient. Additionally, the investigators will utilize a parallel mouse model of HIV mimicking PLWH with stable viral load that can provide mechanistic insight and integrate experiments at the tissue level (adipose tissue) as well. Experiments in the parallel mouse model of HIV will also present the advantage to enable the study the direct effects of HIV viral infection on metabolic and cardiovascular function, a study not feasible in PWH who, for easily understandable ethical reasons, cannot remain without treatment for 6 months (duration of the study).

Study Record Dates

• First Submitted: April 1, 2020
• First Posted: April 9, 2020
• Study Start: September 17, 2020
• Primary Completion: June 17, 2022
• Study Completion: February 25, 2023
• Last Updated: July 27, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Following publication. No end date.
• Access Criteria: To achieve aims in the approved proposal.

Locations

US (1)