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

Adiposity Clinical Trial

— ADIPOSITY  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04675255
• Other study ID #: 202008043
• Status: Completed
• Phase: N/A
• Start date: January 1, 2021
• Est. completion date: June 8, 2023

Study information

• Verified date: August 2023
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: June 8, 2023
• Est. primary completion date: June 8, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adiposity
• HIV I Infection
• Insulin Resistance
• Obesity

Intervention

Procedure:
• Frequently sampled glucose tolerance testing
Frequently sampled glucose tolerance testing
• abdominal subcutaneous adipose tissue biopsy
abdominal subcutaneous adipose tissue biopsy
• MRI scan to assess intrahepatic triglyceride content
MRI scan to assess intrahepatic triglyceride content

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Washington University School of Medicine	Janssen Scientific Affairs, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Intrahepatic triglyceride (IHTG) content measure by magnetic resonance	Change in intrahepatic triglyceride (IHTG) content measured by magnetic resonance imaging (MRI	12 weeks
Secondary	Intrahepatic triglyceride (IHTG) content measure by magnetic resonance	Change in intrahepatic triglyceride (IHTG) content measured by magnetic resonance imaging (MRI	24 weeks
Secondary	Adipocyte size measured by osmium tetroxide fixation technique	Change in adipocyte size by the osmium tetroxide fixation technique	12 weeks
Secondary	Adipocyte size measured by osmium tetroxide fixation technique	Change in adipocyte size by the osmium tetroxide fixation technique	24 weeks
Secondary	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
Secondary	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
Secondary	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