ObesityPhase 2NCT05912621
Tirzepatide: Reversal of Lipotoxicity and Adipose Tissue Dysfunction in Humans With Overweight/Obesity
A Phase 2 study testing Tirzepatide in people with Obesity and Overweight and Obesity, run by Stanford University at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Obesity, Overweight and Obesity, Overweight
- What is being tested?
- Tirzepatide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Nov 2023to Dec 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- nondiabetic as defined by fasting plasma glucose < 126 mg/dL while off all glucose lowering medications
- BMI 27-39.9 kg/m2. Individuals with obesity (BMI 30-39.9 kg/m2) are not required to have an additional risk factor but those who are overweight (27-29.9 kg/m2) must have at least one weight-related factor as follows: hypertension defined as physician-diagnosed and taking antihypertensive medication or SBP> 130 or DBP > 80 mm Hg; dyslipidemia defined as physician diagnosed and taking medication or LDL > 160 mg/dL, TG > 150 mg/dL, HDL < 50 or < 40 mg/dL for women and men, respectively; prediabetes defined as fasting glucose 100-125 mg/dL off all antidiabetic or diabetogenic medications, physician diagnosed obstructive sleep apnea, non-alcoholic fatty liver disease, history of gallstones, and osteoarthritis.
- Age 18-70
- Pre and postmenopausal women will be eligible and details of last menstrual period and/or hormone replacement collected for statistical adjustment and formal testing for effect modification.
Who cannot join
- prior bariatric surgery or liposuction
- unstable body weight defined as self-reported weight change >2 kg over the past 6 weeks
- unstable hypertension (defined as BP >160/100 mm Hg)
- major organ disease
- chronic inflammatory conditions
- pregnancy/lactation
Show all 10Show fewer
- active malignancy undergoing treatment
- use (current or within the past three months) of diabetogenic or weight loss medications, including GLP1 analogs
- active eating or psychiatric disorder
- heavy alcohol use (>2 drinks/day for women and > 3 drinks/day for men) will be excluded
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Clinical and Translational Research Unit
Palo Alto, California, 94305
Nicole Turk, BS, 650-888-0144, nturk@stanford.edu
Tracey McLaughlin, MD
About this study
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.
Read the detailed description
All participants will come to the Stanford University campus for their baseline, week 6, and week 22 (end of study) tests. Prior to starting the assigned intervention, all participants will undergo a supervised (by study dietitian) week of weight maintenance, followed by baseline tests including insulin resistance test (SSPG), Standardized Meal Tolerance Test (for hormone and metabolite profiles), oral glucose tolerance test (OGTT), DXA and MRI scans (to quantify total, regional, and intrahepatic fat), and a subcutaneous periumbilical adipose tissue needle biopsy. Following baseline testing, participants begin tirzepatide vs diet. weight loss will be aggressive for the first six weeks with diet to match the tirzepatide weight loss that is expected. After week 6 weight loss will occur naturally on both without matching. Patients will see the dietitian and coordinator every two weeks to review diet and physical activity, and evaluate tolerability/side effects, and obtain morning weight at Stanford. The metabolic tests, regional fat scans, and biopsy will be repeated at week 6 and week 22.
- Conditions
- Obesity, Overweight and Obesity, Overweight
- Being tested
- Tirzepatide
- Medical subject headings
- Obesity, Overweight
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TirzepatideDrug
Also called Mounjaro
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 group | Role | What they receive |
|---|---|---|
| 2.5 mg (up to 15 mg) Tirzepatide | Experimental | 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). Receives: Drug: Tirzepatide |
| Diet-controlled | No intervention | 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Adipocyte Size
Using a multisizer, we will identify the size and distribution changes of fat cells from baseline to the end of the weight loss period to compare between tirzepatide administration and dietary restriction group
Measured: Baseline and Week 22
Change in Adipocyte Fat Storage Capacity
Using a Oil Red O and rtPCR, we will identify the fat storage capacity of fat cells from baseline to the end of the weight loss period to compare between tirzepatide administration and dietary restriction group
Measured: Baseline and Week 22
Assess changes in Regional Fat
Using a DXA scan, we will measure the percentages of total, upper, lower, truncal, peripheral, and subcutaneous fat and compare it at baseline, 6 weeks, and 22 weeks for each participant
Measured: Baseline, week 6, and week 22
Change from baseline on the 2-stage Steady State Plasma Glucose test
Compare direct measurement of insulin sensitivity after baseline, week 6, and week 22
Measured: Baseline, week 6, and week 22
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2023
- Study start9 Nov 2023
- Primary completionJun 2028 (estimated)
- Study completionDec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ObesityStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 204 patients with BMI 27-39.9 kg/m2 and fasting plasma glucose \< 126 mg/dL will be screened to enroll 68 (to complete 60) who will be randomized 1:1 (computer generated randomization with blocking by sex and BMI category (27-29.9, 30-34.9, 35-39.9 kg/m2) to tirzepatide or dietary weight loss for 22 wks. Individuals with BMI 27-29.9 kg/m2 must have an additional cardiovascular risk factor or weight-related comorbidity.
- Masking
- None (open label)
- Enrolment
- 66 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- Eli Lilly and Company
- Responsible party
- Principal investigator, Tracey McLaughlin, Stanford University
- Investigators
- Tracey McLaughlin, MD, Principal investigator, Stanford School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05912621
- Sponsor's protocol ID
- 70131
- Status last verified
- Dec 2024
- First submitted
- 12 Jun 2023
- Last updated
- 4 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tirzepatide: Reversal of Lipotoxicity and Adipose Tissue Dysfunction in Humans With Overweight/Obesity
- ClinicalTrials.gov ID
- NCT05912621
- Acronym / sponsor ID
- 70131
- Conditions
- Obesity, Overweight and Obesity, Overweight
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 66 participants (estimated)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- Eli Lilly and Company
- Study start
- 9 Nov 2023 (actual)
- Primary completion
- Jun 2028 (estimated)
- Study completion
- Dec 2029 (estimated)
- First posted
- 22 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
All participants will come to the Stanford University campus for their baseline, week 6, and week 22 (end of study) tests. Prior to starting the assigned intervention, all participants will undergo a supervised (by study dietitian) week of weight maintenance, followed by baseline tests including insulin resistance test (SSPG), Standardized Meal Tolerance Test (for hormone and metabolite profiles), oral glucose tolerance test (OGTT), DXA and MRI scans (to quantify total, regional, and intrahepatic fat), and a subcutaneous periumbilical adipose tissue needle biopsy. Following baseline testing, participants begin tirzepatide vs diet. weight loss will be aggressive for the first six weeks with diet to match the tirzepatide weight loss that is expected. After week 6 weight loss will occur naturally on both without matching. Patients will see the dietitian and coordinator every two weeks to review diet and physical activity, and evaluate tolerability/side effects, and obtain morning weight at Stanford. The metabolic tests, regional fat scans, and biopsy will be repeated at week 6 and week 22.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 204 patients with BMI 27-39.9 kg/m2 and fasting plasma glucose < 126 mg/dL will be screened to enroll 68 (to complete 60) who will be randomized 1:1 (computer generated randomization with blocking by sex and BMI category (27-29.9, 30-34.9, 35-39.9 kg/m2) to tirzepatide or dietary weight loss for 22 wks. Individuals with BMI 27-29.9 kg/m2 must have an additional cardiovascular risk factor or weight-related comorbidity.
| Arm | Type | Receives |
|---|---|---|
| 2.5 mg (up to 15 mg) Tirzepatide | Experimental | Drug: TirzepatidePatients 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). |
| Diet-controlled | No intervention | –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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- nondiabetic as defined by fasting plasma glucose < 126 mg/dL while off all glucose lowering medications
- BMI 27-39.9 kg/m2. Individuals with obesity (BMI 30-39.9 kg/m2) are not required to have an additional risk factor but those who are overweight (27-29.9 kg/m2) must have at least one weight-related factor as follows: hypertension defined as physician-diagnosed and taking antihypertensive medication or SBP> 130 or DBP > 80 mm Hg; dyslipidemia defined as physician diagnosed and taking medication or LDL > 160 mg/dL, TG > 150 mg/dL, HDL < 50 or < 40 mg/dL for women and men, respectively; prediabetes defined as fasting glucose 100-125 mg/dL off all antidiabetic or diabetogenic medications, physician diagnosed obstructive sleep apnea, non-alcoholic fatty liver disease, history of gallstones, and osteoarthritis.
- Age 18-70
- Pre and postmenopausal women will be eligible and details of last menstrual period and/or hormone replacement collected for statistical adjustment and formal testing for effect modification.
Key exclusion criteria (10 listed)
- prior bariatric surgery or liposuction
- unstable body weight defined as self-reported weight change >2 kg over the past 6 weeks
- unstable hypertension (defined as BP >160/100 mm Hg)
- major organ disease
- chronic inflammatory conditions
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TirzepatideAlso: MounjaroTirzepatide 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. | Drug | 2.5 mg (up to 15 mg) Tirzepatide |
Primary outcome
Change in Adipocyte Size
Time frame: Baseline and Week 22
Using a multisizer, we will identify the size and distribution changes of fat cells from baseline to the end of the weight loss period to compare between tirzepatide administration and dietary restriction group
Change in Adipocyte Fat Storage Capacity
Time frame: Baseline and Week 22
Using a Oil Red O and rtPCR, we will identify the fat storage capacity of fat cells from baseline to the end of the weight loss period to compare between tirzepatide administration and dietary restriction group
Assess changes in Regional Fat
Time frame: Baseline, week 6, and week 22
Using a DXA scan, we will measure the percentages of total, upper, lower, truncal, peripheral, and subcutaneous fat and compare it at baseline, 6 weeks, and 22 weeks for each participant
Change from baseline on the 2-stage Steady State Plasma Glucose test
Time frame: Baseline, week 6, and week 22
Compare direct measurement of insulin sensitivity after baseline, week 6, and week 22
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Tracey McLaughlin, MD principal investigator
Stanford School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tirzepatide in people with Obesity and Overweight and Obesity, run by Stanford University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nicole Turk, BS (6508880144, nturk@stanford.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Adipocyte Size (time frame: Baseline and Week 22). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2024.