Clinical trial NCT04675255: Assessing the Impact of INSTI to PI Switch on Insulin Sensitivity and Fat Metabolism
Official title: WU 360: Assessing the Impact of Integrase Strand Transfer Inhibitors (INSTI) to Protease Inhibitor (PI) Switch on Insulin Sensitivity and Fat Metabolism (ADIPOSITY): a Sub-study of DEFINE
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV I Infection
Adiposity
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: Janssen Scientific Affairs, LLC
First posted: 2020-12-19
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: A substudy of TMC114FD2HTX4004 that will perform glucose tolerance testing, adipose testing and MRI scan at baseline, 12 and 24 weeks post switch of ART medications.

Detailed description: Synopsis Full study title: Assessing the impact of integrase strand transfer inhibitors (INSTI) to protease inhibitor (PI) switch on insulin sensitivity and fat metabolism (ADIPOSITY): a sub-study of DEFINE

Endpoints and objectives:

The following endpoints will be determined 12 and 24 weeks after switch from an INSTI-based antiretroviral therapy (ART) regimen to a PI-based regimen:

Primary endpoint: Change in insulin sensitivity (SI) at 12 weeks assessed by using a 3-hour frequently sampled oral glucose tolerance testing (fsOGTT).

Secondary endpoints: 1) Change in insulin sensitivity (SI) at 24 weeks assessed by using a 3-hour frequently sampled oral glucose tolerance testing (fsOGTT); 2) Change in insulin secretion during the fsOGTT assessed by using C-peptide deconvolution; 3) Change in intrahepatic triglyceride (IHTG) content measured by magnetic resonance imaging (MRI); 4) Change in adipocyte size by the osmium tetroxide fixation technique; and 5) Change in expression of genes associated with adipose tissue development, lipogenesis, inflammation and endocrine function by RNA sequencing.

Hypothesis: Insulin sensitivity will improve following switch from INSTIs to PIs

Eligibility criteria: Inclusion Criteria:

* • Must be enrolled in the DEFINE study TMC114FD2HTX4004

  * Must sign an ICF indicating that they understand the purpose of, and procedures required for, the study and are willing to participate in the study.

Exclusion Criteria:

* • Contraindication to magnetic resonance imaging as determined by institutional policy.

  * Current diagnosis of diabetes mellitus

Primary outcomes:
measure: Insulin Sensitivity measured by homeostatic model assessment for insulin resistance {HOMA_IR}
timeFrame: 12 weeks
Secondary outcomes:
measure: Intrahepatic triglyceride (IHTG) content measure by magnetic resonance
timeFrame: 12 weeks
measure: Intrahepatic triglyceride (IHTG) content measure by magnetic resonance
timeFrame: 24 weeks
measure: Adipocyte size measured by osmium tetroxide fixation technique
timeFrame: 12 weeks
measure: Adipocyte size measured by osmium tetroxide fixation technique
timeFrame: 24 weeks
measure: Adipocyte gene expression correlated with adipose tissue development
timeFrame: 12 weeks
measure: Adipocyte gene expression correlated with adipose tissue development
timeFrame: 24 weeks
measure: Insulin Sensitivity measured by homeostatic model assessment for insulin resistance {HOMA_IR}
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine in St. Louis
name: Jane O'Halloran, MB BA PhD
role: PRINCIPAL_INVESTIGATOR
References: