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Insulin Regulation of Lipolysis and Lipolysis Proteins

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ClinicalTrials.gov Identifier: NCT03866408
Recruitment Status : Recruiting
First Posted : March 7, 2019
Last Update Posted : June 5, 2019
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Michael D. Jensen, Mayo Clinic

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.

Condition or disease Intervention/treatment Phase
Obesity Behavioral: Immediate weight loss Drug: Pioglitazone Behavioral: Deferred weight loss Drug: Placebo Early Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 64 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Basic Science
Official Title: Insulin Regulation of Lipolysis and Lipolysis Proteins
Actual Study Start Date : November 12, 2018
Estimated Primary Completion Date : September 1, 2020
Estimated Study Completion Date : September 1, 2021

Resource links provided by the National Library of Medicine


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

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.

Drug: Pioglitazone
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.




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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. 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.



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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03866408


Locations
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United States, Minnesota
Mayo Clinic in Rochester Recruiting
Rochester, Minnesota, United States, 55905
Contact: Pamela A Reich    507-255-6062    reich.pamela@mayo.edu   
Sponsors and Collaborators
Mayo Clinic
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
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Principal Investigator: Michael D Jensen Mayo Clinic

Additional Information:
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Responsible Party: Michael D. Jensen, Principal Investigator, Mayo Clinic
ClinicalTrials.gov Identifier: NCT03866408     History of Changes
Other Study ID Numbers: 17-009837
2R01DK040484-30 ( U.S. NIH Grant/Contract )
First Posted: March 7, 2019    Key Record Dates
Last Update Posted: June 5, 2019
Last Verified: March 2019

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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
Keywords provided by Michael D. Jensen, Mayo Clinic:
adipose tissue
Additional relevant MeSH terms:
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Pioglitazone
Hypoglycemic Agents
Physiological Effects of Drugs