Insulin Regulation of Lipolysis and Lipolysis Proteins

October 19, 2023 updated by: Michael D. Jensen, Mayo Clinic
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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

  1. The investigators will determine whether impaired insulin-induced suppression of lipolysis (as measured by IC50) is related to the above mentioned lipolysis proteins in groups of volunteers known to vary widely with regards to abdominal adipocyte size and regulation of adipose tissue lipolysis.
  2. The investigators will determine whether the improved insulin regulation of lipolysis resulting from treatment with the PPARγ agonist pioglitazone, with or without weight loss, can be linked to specific changes in sets of PPARγ-responsive adipocyte lipolysis proteins in UBO adults.

Study Type

Interventional

Enrollment (Estimated)

64

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Mayo Clinic in Rochester
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • 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

Exclusion Criteria, Pioglitazone package insert of contraindications for use:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Immediate weight loss - placebo
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
Upper body obese subjects will undergo behavioral intervention with a life coach and a physical activity program of their choice for 4 months.
Drug: Placebo
Upper body obese subjects will be block randomized to pioglitazone or placebo at enrollment.
Placebo Comparator: Deferred control group - placebo
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.
Drug: Placebo
Upper body obese subjects will be block randomized to pioglitazone or placebo at enrollment.
Behavioral: Deferred weight loss
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.
Active Comparator: Immediate weight loss - pioglitazone
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
Upper body obese subjects will undergo behavioral intervention with a life coach and a physical activity program of their choice for 4 months.
Drug: Pioglitazone
Upper body obese subjects will be block randomized to pioglitazone or placebo at enrollment.
Active Comparator: Deferred group - pioglitazone

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.
Behavioral: Deferred weight loss
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.
Drug: Pioglitazone
Upper body obese subjects will be block randomized to pioglitazone or placebo at enrollment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adipocyte response to insulin - perilipin 1 and FSP27 relative to HSL and ATGL
Time Frame: 4-9 months
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.
Time Frame: 4-9 months
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
Time Frame: 4-9 months
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
Time Frame: 4-9 months
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mayo Clinic

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

  • Principal Investigator: Michael D Jensen, Mayo Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 12, 2018

Primary Completion (Estimated)

December 1, 2024

Study Completion (Estimated)

December 1, 2024

Study Registration Dates

First Submitted

December 13, 2018

First Submitted That Met QC Criteria

March 5, 2019

First Posted (Actual)

March 7, 2019

Study Record Updates

Last Update Posted (Actual)

October 23, 2023

Last Update Submitted That Met QC Criteria

October 19, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 17-009837
  • 2R01DK040484-30 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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