Assessing the Impact of INSTI to PI Switch on Insulin Sensitivity and Fat Metabolism

Not Applicable

Completed

• Conditions: Adiposity; HIV I Infection
• Interventions: Procedure: Frequently sampled glucose tolerance testing; Procedure: abdominal subcutaneous adipose tissue biopsy; Procedure: MRI scan to assess intrahepatic triglyceride content

• Registration Number: NCT04675255
• Lead Sponsor: Washington University School of Medicine

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

Study Timeline

• Study First Submitted: 2020-10-13
• Study First Submitted QC: 2020-12-14
• Study First Posted: 2020-12-19
• Study Start: 2021-01-01
• Primary Completion: 2023-06-08
• Study Completion: 2023-06-08
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-01
• Last Update Posted: 2023-08-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 8

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Delayed switch	MRI scan to assess intrahepatic triglyceride content	Delayed switch
Immediate switch	abdominal subcutaneous adipose tissue biopsy	Immediate switch
Immediate switch	MRI scan to assess intrahepatic triglyceride content	Immediate switch
Delayed switch	abdominal subcutaneous adipose tissue biopsy	Delayed switch
Immediate switch	Frequently sampled glucose tolerance testing	Immediate switch
Delayed switch	Frequently sampled glucose tolerance testing	Delayed switch

Primary Outcome Measures

Name	Time	Method
Insulin Sensitivity measured by homeostatic model assessment for insulin resistance {HOMA_IR}	12 weeks	Change in insulin sensitivity (SI) at 12 weeks assessed by using a 3-hour frequently sampled oral glucose tolerance testing (fsOGTT).to calculate HOMA_IR

Secondary Outcome Measures

Name	Time	Method
Adipocyte gene expression correlated with adipose tissue development	24 weeks	Change in expression of adipose tissue genes correlated with adipose tissue development, lipogenesis, inflammation and endocrine function measured by RNA sequencing
Adipocyte size measured by osmium tetroxide fixation technique	24 weeks	Change in adipocyte size by the osmium tetroxide fixation technique
Insulin Sensitivity measured by homeostatic model assessment for insulin resistance {HOMA_IR}	24 weeks	Change in insulin sensitivity (SI) at 12 weeks assessed by using a 3-hour frequently sampled oral glucose tolerance testing (fsOGTT).to calculate HOMA_IR
Intrahepatic triglyceride (IHTG) content measure by magnetic resonance	24 weeks	Change in intrahepatic triglyceride (IHTG) content measured by magnetic resonance imaging (MRI

Trial Locations

Locations (1)

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States