Normal-weight Diabetes: Adipocyte-directed Therapy with Pioglitazone or Tirzepatide

NCT ID: NCT06657209

Last Updated: 2024-10-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE4

Total Enrollment

104 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-12-15

Study Completion Date

2027-12-15

Brief Summary

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This study is to investigate how adipocyte (fat cell) function and fat distribution differ between individuals with normal-weight type 2 diabetes (NWD) and normal-weight controls without diabetes (NWC). The study will assess whether adipocyte-directed therapies, specifically pioglitazone and tirzepatide, can improve insulin resistance, adipocyte function, and fat distribution in individuals with NWD. By analyzing the biological mechanisms underlying adipocyte dysfunction, the study aims to provide insights into novel treatment strategies for improving metabolic health in normal-weight individuals with type 2 diabetes.

Detailed Description

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The investigators aim to learn how adipocyte dysfunction and disordered fat distribution contribute to the development of type 2 diabetes in normal-weight individuals. The investigators hope to determine whether adipocyte-directed therapies, such as pioglitazone and tirzepatide, can improve insulin sensitivity, fat distribution, and metabolic health in this population. This study is important because most diabetes research focuses on overweight or obese individuals, and very little is known about how diabetes affects those with normal body weight. Understanding the unique biology of normal-weight diabetes could lead to more personalized and effective treatment strategies, filling a gap in diabetes care for a group that can be overlooked in clinical research.

Conditions

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Diabetes Mellitus, Type 2

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Control group will undergo baseline testing to provide information about people without diabetes, but will not proceed with treatment.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Normal weight controls

Control

Group Type OTHER

Insulin resistance testing

Intervention Type PROCEDURE

Steady state Plasma Glucose test

OGTT

Intervention Type PROCEDURE

Will collect 5 blood draws during the test to measure insulin secretion

Fat biopsy

Intervention Type PROCEDURE

Needle biopsy to gather a sample of abdominal subcutaneous fat

DXA scan

Intervention Type RADIATION

Whole body DXA scan

MRI

Intervention Type PROCEDURE

Abdominal MRI

1H-MRS

Intervention Type PROCEDURE

Spectroscopy of the abdominal region

Normal weight with diabetes tirzepatide first pioglitazone second

Baseline testing Intervention with tirzepatide for 16 weeks Retesting Washout for 5 weeks Intervention with pioglitazone for 16 weeks Retesting

Group Type EXPERIMENTAL

Insulin resistance testing

Intervention Type PROCEDURE

Steady state Plasma Glucose test

OGTT

Intervention Type PROCEDURE

Will collect 5 blood draws during the test to measure insulin secretion

Fat biopsy

Intervention Type PROCEDURE

Needle biopsy to gather a sample of abdominal subcutaneous fat

DXA scan

Intervention Type RADIATION

Whole body DXA scan

MRI

Intervention Type PROCEDURE

Abdominal MRI

1H-MRS

Intervention Type PROCEDURE

Spectroscopy of the abdominal region

Tirzepatide

Intervention Type DRUG

16 weeks started at 2.5mg/week and increased to 5mg/week dose

Pioglitazone

Intervention Type DRUG

16 weeks at a 45mg/day dose

Normal weight with diabetes pioglitazone first, tirzepatide second

Baseline testing Intervention with pioglitazone for 16 weeks Retesting Washout for 5 weeks Intervention with tirzepatide for 16 weeks Retesting

Group Type EXPERIMENTAL

Insulin resistance testing

Intervention Type PROCEDURE

Steady state Plasma Glucose test

OGTT

Intervention Type PROCEDURE

Will collect 5 blood draws during the test to measure insulin secretion

Fat biopsy

Intervention Type PROCEDURE

Needle biopsy to gather a sample of abdominal subcutaneous fat

DXA scan

Intervention Type RADIATION

Whole body DXA scan

MRI

Intervention Type PROCEDURE

Abdominal MRI

1H-MRS

Intervention Type PROCEDURE

Spectroscopy of the abdominal region

Tirzepatide

Intervention Type DRUG

16 weeks started at 2.5mg/week and increased to 5mg/week dose

Pioglitazone

Intervention Type DRUG

16 weeks at a 45mg/day dose

Interventions

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Insulin resistance testing

Steady state Plasma Glucose test

Intervention Type PROCEDURE

OGTT

Will collect 5 blood draws during the test to measure insulin secretion

Intervention Type PROCEDURE

Fat biopsy

Needle biopsy to gather a sample of abdominal subcutaneous fat

Intervention Type PROCEDURE

DXA scan

Whole body DXA scan

Intervention Type RADIATION

MRI

Abdominal MRI

Intervention Type PROCEDURE

1H-MRS

Spectroscopy of the abdominal region

Intervention Type PROCEDURE

Tirzepatide

16 weeks started at 2.5mg/week and increased to 5mg/week dose

Intervention Type DRUG

Pioglitazone

16 weeks at a 45mg/day dose

Intervention Type DRUG

Other Intervention Names

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SSPG Oral glucose tolerance test proton magnetic resonance spectroscopy Mounjaro Actos

Eligibility Criteria

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Inclusion Criteria

Normal-Weight Diabetes (NWD) Group:

1. Age: 30 to 70 years old.
2. Diagnosis of Type 2 Diabetes (T2D): Based on a previous diagnosis or confirmed by laboratory testing at screening (A1c \> 5.7% or fasting glucose \> 100 mg/dL).
3. HbA1c Range: Between 5.7% and 8%, with a stable medication or lifestyle regimen for at least 3 months.
4. BMI: Between 19 and 24.9 kg/m².
5. Diabetes Medications: All diabetes medications are allowed, except insulin and pioglitazone. GLP-1 receptor agonists are permitted if the dose has been stable for 3 months.
6. Stable Body Weight: Body weight must have been stable (no more than 2 kg change) over the last 3 months.

Normal-Weight Control (NWC) Group:

1. Age: 30 to 70 years old.
2. No Diagnosis of Diabetes: Fasting plasma glucose \< 100 mg/dL and A1c \< 5.7%, with no history of glucose-lowering medications.
3. BMI: Between 19 and 24.9 kg/m².
4. Stable Body Weight: No more than 2 kg change over the past 3 months. -

Exclusion Criteria

1. Pregnancy or Lactation: Women who are pregnant, planning to become pregnant, or breastfeeding are excluded due to potential risks to the fetus or infant.
2. Prior Use of Pioglitazone: Participants who have previously used pioglitazone are excluded to avoid confounding effects of prior drug exposure.
3. Unstable Body Weight: Individuals with a body weight change of more than 2 kg in the last 3 months are excluded to ensure stable metabolic conditions.
4. Liver or Kidney Disease: Participants with significant liver disease (ALT \> 3x upper limit of normal) or renal disease (creatinine \> 1.5 mg/dL) are excluded due to potential safety risks.
5. Congestive Heart Failure or Fluid Overload History: These conditions are exclusionary due to the risk of fluid retention with pioglitazone.
6. Uncontrolled Hypertension: Blood pressure \> 160/90 mmHg excludes participants due to increased cardiovascular risk.
7. Active Cancer: Individuals with a diagnosis of cancer in the past 3 years (except for skin cancer) are excluded.
8. Chronic Inflammatory Diseases: Excluded due to potential effects on metabolic measurements.
9. Use of Weight Loss Medications: Those currently taking weight loss medications are excluded to prevent confounding effects on body weight and metabolic function.
10. Bariatric Surgery or Liposuction History: Participants who have had weight-loss surgeries or liposuction are excluded due to alterations in fat tissue and metabolic profiles.
11. Insulin Use: Participants using insulin are excluded to focus on non-insulin-dependent diabetes.
12. Active Psychiatric Disease or Eating Disorders: Individuals with these conditions are excluded due to potential impacts on study compliance and data integrity.
13. Substance Abuse: Participants with a history of substance abuse are excluded for similar reasons.

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Minimum Eligible Age

30 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Stanford University

OTHER

Sponsor Role lead

Responsible Party

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Tracey McLaughlin

Professor of Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Stanford University, Clinical and Translational Research Unit (CTRU)

Stanford, California, United States

Site Status

Countries

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United States

Central Contacts

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Alina Choi, BS

Role: CONTACT

(650) 725-9865

Jasmine Yang, BS

Role: CONTACT

(401) 601-8851

Facility Contacts

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Alina Choi, BS

Role: primary

(650) 723-6713

Jasmine Yang, BS

Role: backup

(401) 601-8851

Tracey McLaughlin, MD

Role: backup

Other Identifiers

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77199

Identifier Type: -

Identifier Source: org_study_id

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