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

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

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.

Study Overview

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

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 Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Immediate switch	Procedure: Frequently sampled glucose tolerance testing; Frequently sampled glucose tolerance testing; Procedure: abdominal subcutaneous adipose tissue biopsy; abdominal subcutaneous adipose tissue biopsy; Procedure: MRI scan to assess intrahepatic triglyceride content; MRI scan to assess intrahepatic triglyceride content
Active Comparator: Delayed switch	Procedure: Frequently sampled glucose tolerance testing; Frequently sampled glucose tolerance testing; Procedure: abdominal subcutaneous adipose tissue biopsy; abdominal subcutaneous adipose tissue biopsy; Procedure: MRI scan to assess intrahepatic triglyceride content; MRI scan to assess intrahepatic triglyceride content

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin Sensitivity measured by homeostatic model assessment for insulin resistance {HOMA_IR}	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	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intrahepatic triglyceride (IHTG) content measure by magnetic resonance	Change in intrahepatic triglyceride (IHTG) content measured by magnetic resonance imaging (MRI	12 weeks
Intrahepatic triglyceride (IHTG) content measure by magnetic resonance	Change in intrahepatic triglyceride (IHTG) content measured by magnetic resonance imaging (MRI	24 weeks
Adipocyte size measured by osmium tetroxide fixation technique	Change in adipocyte size by the osmium tetroxide fixation technique	12 weeks
Adipocyte size measured by osmium tetroxide fixation technique	Change in adipocyte size by the osmium tetroxide fixation technique	24 weeks
Adipocyte gene expression correlated with adipose tissue development	Change in expression of adipose tissue genes correlated with adipose tissue development, lipogenesis, inflammation and endocrine function measured by RNA sequencing	12 weeks
Adipocyte gene expression correlated with adipose tissue development	Change in expression of adipose tissue genes correlated with adipose tissue development, lipogenesis, inflammation and endocrine function measured by RNA sequencing	24 weeks
Insulin Sensitivity measured by homeostatic model assessment for insulin resistance {HOMA_IR}	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	24 weeks

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: Janssen Scientific Affairs, LLC
• Investigators: Principal Investigator: Jane O'Halloran, MB BA PhD, Washington University School of Medicine in St. Louis

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Actual): June 8, 2023
• Study Completion (Actual): June 8, 2023

Study Registration Dates

• First Submitted: October 13, 2020
• First Submitted That Met QC Criteria: December 14, 2020
• First Posted (Actual): December 19, 2020

Study Record Updates

• Last Update Posted (Actual): August 3, 2023
• Last Update Submitted That Met QC Criteria: August 1, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Hyperinsulinism; Obesity; Insulin Resistance
• Other Study ID Numbers: 202008043

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No