Insulin Regulation of Lipolysis and Lipolysis Proteins

Mayo Clinic

Status and phase: Enrolling; Early Phase 1

Conditions: Obesity

Treatments: Drug: Placebo; Behavioral: Deferred weight loss; Behavioral: Immediate weight loss; Drug: Pioglitazone

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03866408

17-009837

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

Details and patient eligibility

About

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.

Full 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.

Enrollment: 64 estimated patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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64 participants in 4 patient groups, including a placebo group

Immediate weight loss - placebo

Active Comparator group

Description:

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.

Treatment:

Behavioral: Immediate weight loss

Drug: Placebo

Deferred control group - placebo

Placebo Comparator group

Description:

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.

Treatment:

Behavioral: Deferred weight loss

Drug: Placebo

Immediate weight loss - pioglitazone

Active Comparator group

Description:

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.

Treatment:

Drug: Pioglitazone

Behavioral: Immediate weight loss

Deferred group - pioglitazone

Active Comparator group

Description:

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.

Treatment:

Drug: Pioglitazone

Behavioral: Deferred weight loss