HIV I Infection, Adiposity
Conditions
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
Interventions
PROCEDUREFrequently sampled glucose tolerance testing
Frequently sampled glucose tolerance testing
abdominal subcutaneous adipose tissue biopsy
PROCEDUREMRI scan to assess intrahepatic triglyceride content
MRI scan to assess intrahepatic triglyceride content
Sponsors
Janssen Scientific Affairs, LLC
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Intrahepatic triglyceride (IHTG) content measure by magnetic resonance | 12 weeks | Change in intrahepatic triglyceride (IHTG) content measured by magnetic resonance imaging (MRI |
| Adipocyte size measured by osmium tetroxide fixation technique | 12 weeks | Change in adipocyte size by the osmium tetroxide fixation technique |
| Adipocyte gene expression correlated with adipose tissue development | 12 weeks | Change in expression of adipose tissue genes correlated with adipose tissue development, lipogenesis, inflammation and endocrine function measured by RNA sequencing |
| 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 |
Countries
United States
Outcome results
None listed