Tirzepatide: Reversal of Lipotoxicity and Adipose Tissue Dysfunction in Humans With Overweight/Obesity

Part of paid clinical trials in Palo Alto, California.

Sponsor
Stanford University
Study ID
NCT05912621
Phase
PHASE2
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 70 Years
Healthy Volunteers
Accepted

Interventions

  • Tirzepatide — DRUG
    Tirzepatide dose is titrated up by 2.5 mg every four weeks as per below, starting with 2.5 mg weekly and maxing out at 15 mg.

Study Details

Obesity, affecting 40% of US adults and costing 173b annually, represents a significant health care burden (1). It is associated with increased risk for multiple chronic diseases including hypertension, type 2 diabetes (T2D), cardiovascular disease, and NAFLD, as well as cancer, osteoarthritis, and obstructive sleep apnea. The investigators plan to test the hypothesis that tirzepatide, a dual GLP/GIP agonist, improves metabolic health (insulin resistance and regional fat distribution and cardiovascular risk profile) not only by inducing weight loss via GLP1-agonism, but also via beneficial cellular and molecular changes in adipose tissue, given that GIP binds receptors in human fat cells. Based on studies in mice showing that GIP alone or tirzepitide treatment decreases inflammation, increases lipid buffering (fat storage in the fat cells instead of releasing it into the bloodstream), and improves glucose homeostasis. The investigators believe that the GIP component of tirzepatide will make fat cells healthier and reverse lipotoxicity, which is one of the mechanisms by which obesity leads to insulin resistance, disordered regional fat distribution, and type 2 diabetes. To date, the effect of dual GLP1 and GIP agonist treatment on adipose tissue has not been evaluated in humans. Given the existing but limited data, dual GIP/GLP-1 agonist treatment in obese humans with metabolic risk factors is an attractive pharmacologic candidate that would lead to both weight loss and healthier fat, potentially offering uniquely powerful synergistic clinical benefits. It is thus of tremendous importance to define the biological effects of dual-agonist treatment on human adipose tissue structure and function, as well as related improvements in regional fat distribution and systemic adipose and muscle insulin sensitivity. In this study, the investigators will randomize overweight (with risk factors) or obese nondiabetic individuals to hypocaloric diet or tirzepatide for 22 weeks with matched weight loss for the first 6 weeks. The investigators will quantify insulin resistance, fat and lean mass, including regional fat distribution, and changes in adipose tissue (needle biopsy from abdominal fat tissue) to see if tirzepatide effects differ from dietary weight loss.

Key Dates

Start date
Nov 9, 2023
Status verified
Dec 2024
Primary completion
Jun 30, 2028
Completion
Dec 31, 2029

Study Design

Enrollment
66 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: 2.5 mg (up to 15 mg) Tirzepatide
    Patients assigned to tirzepatide will undergo dose titration starting with 2.5 mg per day with an increase every four weeks if tolerated by nausea. During the first 6 weeks, weight loss must be matched with the dietary weight loss arm at 0.6 kg/week. Participants will be seen every two weeks to review diet and physical activity, evaluate tolerability/side effects, and obtain morning weight. If weight loss is greater than 0.6 kg/week, recommendations to increase caloric intake will be made through the week 6 visits that repeat baseline testings (biopsy, metabolic tests, and regional fat scans). After the 6th week, weight loss can occur naturally without any restrictions (no further matching to the dietary weight loss group is required). Starting at week 8 the visits are decreased to every 4 weeks. Biopsies, metabolic tests, and regional fat scans are completed at baseline, week 6, and end of study (week 22).
  • No Intervention: Diet-controlled
    The group assigned to dietary weight loss will undergo intensive dietary counseling with initial 3 day food diary evaluation followed by specific dietary recommendations that include macronutrient balanced, healthful and calorie-restricted diet, weekly dietitian visits, alternating between video and in person, use of a mobile app for food logging, weekly weights at home and biweekly weights, and review of these data by the study dietitian who will give individualized feedback at the weekly visits in order to attain targeted weight loss of 0.6 kg per week. The goal is to match weight loss in the tirzepatide and diet groups for the first six weeks. Any residual differences in weight loss at 6 weeks will be adjusted statistically. At six weeks all baseline tests (biopsy, metabolic tests, and regional fat scans) will be repeated, after which no further attempts for matching for weight loss will occur. At the end of the study (week 22), all baseline testing will occur again.

Primary Outcome Measure

Change in Adipocyte Size [ Time Frame: Baseline and Week 22 ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
Clinical and Translational Research UnitPalo AltoCalifornia94305
Nicole Turk, BS
[email protected]
650-888-0144
Tracey McLaughlin, MD (PRINCIPAL_INVESTIGATOR)

Find similar trials in Palo Alto, CA

By condition
Obesity / overweight
By specialty
EndocrinologyMetabolic healthWeight loss
By research site
Clinical and Translational Research Unit· Palo Alto, CA

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