Insulin Regulation of Lipolysis and Lipolysis Proteins

NCT03866408 | Recruiting Early Phase 1 FDA Drug

• 2 other identifiers: 17-0098372R01DK040484-30
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

These studies will define the abnormalities in the adipocyte proteins that are involved in the failure of insulin to suppress lipolysis normally in humans with upper body obesity and will help discover the mechanism by which pioglitazone, a medication used to treat type 2 diabetes and improve insulin resistance, improves insulin-regulation of adipocyte fatty acid metabolism.

Conditions

Obesity

Keywords

adipose tissue

Outcome Measures

Primary Outcomes (4)

• Adipocyte response to insulin - perilipin 1 and FSP27 relative to HSL and ATGL

  In response to weight maintenance vs. weight loss with pioglitazone vs. placebo, insulin regulation of lipolysis in upper body obese as measured by insulin IC50 for palmitate flux and compared to adipocyte perilipin 1 and FSP27 relative to HSL and ATGL.

  4-9 months

• Adipocyte response to insulin - adipocyte G0S2 relative to ATGL.

  In response to weight maintenance vs. weight loss with pioglitazone vs. placebo, insulin regulation of lipolysis in upper body obese as measured by insulin IC50 for palmitate flux and compared to adipocyte G0S2 relative to ATGL.

  4-9 months

• Adipocyte response to insulin - adipocyte CGI-58 relative to ATGL

  In response to weight maintenance vs. weight loss with pioglitazone vs. placebo, insulin regulation of lipolysis in upper body obese as measured by insulin IC50 for palmitate flux and compared to adipocyte CGI-58 relative to ATGL.

  4-9 months

• Adipocyte response to insulin - perilipin 1, ATGL and HSL phosphorylation

  In response to weight maintenance vs. weight loss with pioglitazone vs. placebo, insulin regulation of lipolysis in upper body obese as measured by insulin IC50 for palmitate flux and compared to adipocyte perilipin 1, ATGL and HSL phosphorylation in response to insulin.

  4-9 months

Study Arms (4)

Immediate weight loss - placebo

ACTIVE COMPARATOR

Upper body obese participants randomized to this group; all will begin their immediate participation in a comprehensive lifestyle obesity treatment program after completion of baseline studies. Half of the volunteers will be randomized to placebo during this period.

Behavioral: Immediate weight loss; Drug: Placebo

Deferred control group - placebo

PLACEBO COMPARATOR

After baseline studies, UBO participants randomized to this group will wait without any intervention for 4 months, with continued monitoring to assure weight stability - this group will be the half of volunteers randomized to deferred weight loss intervention that are also randomized to placebo. At the end of this 'wait' period they will be enrolled in the same comprehensive lifestyle obesity treatment program for 4 months, but without placebo.

Behavioral: Deferred weight loss; Drug: Placebo

Immediate weight loss - pioglitazone

ACTIVE COMPARATOR

Upper body obese participants randomized to this group; all will begin their immediate participation in a comprehensive lifestyle obesity treatment program after completion of baseline studies. Half of the volunteers will be randomized to pioglitazone during this period.

Behavioral: Immediate weight loss; Drug: Pioglitazone

Deferred group - pioglitazone

ACTIVE COMPARATOR

After baseline studies, UBO participants randomized to this group will wait without any intervention for 4 months, with continued monitoring to assure weight stability - this group will be the half of volunteers randomized to deferred weight loss intervention that are randomized to pioglitazone. They will be monitored to prevent the usual but modest weight gain associated with pioglitazone. They will be on pioglitazone during the 'wait' period. At the end of this 'wait' period they will be enrolled in the same comprehensive lifestyle obesity treatment program for 4 months, but without pioglitazone.

Drug: Pioglitazone; Behavioral: Deferred weight loss

Interventions

Immediate weight loss BEHAVIORAL

Upper body obese subjects will undergo behavioral intervention with a life coach and a physical activity program of their choice for 4 months.

Immediate weight loss - pioglitazone; Immediate weight loss - placebo

Pioglitazone DRUG

Upper body obese subjects will be block randomized to pioglitazone or placebo at enrollment.

Deferred group - pioglitazone; Immediate weight loss - pioglitazone

Deferred weight loss BEHAVIORAL

Upper body obese subjects will complete a weight-stable period of 4 months and subsequently undergo behavioral intervention with a life coach and a physical activity program of their choice for 4 months.

Deferred control group - placebo; Deferred group - pioglitazone

Placebo DRUG

Upper body obese subjects will be block randomized to pioglitazone or placebo at enrollment.

Deferred control group - placebo; Immediate weight loss - placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Men and Women between the ages of 18 and 55.
• Women will be premenopausal
• Non obese adults BMI between 18-25
• Obese BMI 30-38

You may not qualify if:

• Initiation in patients with established New York Heart Associations (NYHA) class III or IV Heart failure.
• Use in patients with known hypersensitivity to pioglitazone or any other component of ACTOSE.

Sponsors & Collaborators

• Mayo Clinic: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Obesity

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Michael D Jensen

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: immediate weight loss (placebo) will be compared with deferred weight loss (placebo) to determine the effects of weight loss alone immediate weight loss placebo will be compared with deferred weight loss pioglitazone to determine the effects of weight loss vs. pioglitazone deferred weight loss placebo will be compared with deferred weight loss pioglitazone to determine the effects of pioglitazone alone deferred weight loss placebo will be compared with deferred weight loss pioglitazone to determine the effects of weight loss alone vs. previous exposure to pioglitazone immediate weight loss placebo and deferred weight loss placebo will be pooled to create a larger group to determine the effects of weight loss on outcome variables

Study Record Dates

• First Submitted: December 13, 2018
• First Posted: March 7, 2019
• Study Start: November 12, 2018
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 28, 2026

Record last verified: 2026-01

Locations

US (1)