Effect of Tirzepatide Plus Intensive Lifestyle Therapy on Body Weight and Metabolic Health in Latinos With Obesity

Study Overview
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Brief Summary
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The purpose of this study is to conduct a three-arm 52-week, randomized controlled trial with double blind treatment to evaluate the effects of a drug called tirzepatide in combination with an innovative, culturally-appropriate, intensive lifestyle intervention (ILI) delivered by community health workers (CHWs) in Latino adults with obesity. Participants will be randomized to 1) standard care (SC, n=25); 2) culturally-tailored dietary and behavioral intensive lifestyle intervention (ILI, n=25) provided by CHWs plus placebo; or 3) ILI plus tirzepatide (ILI-TRZ) for 52 weeks to evaluate the intervention's effect on: i) weight loss; ii) clinical efficacy (change in body fat mass, liver fat, intra-abdominal fat mass and intrahepatic triglyceride content, oral glucose tolerance, glycemic control, insulin sensitivity and b-cell function, plasma lipids, blood pressure, sleep duration, quality and behaviors, physical performance scores); iii) adherence and fidelity to the intervention (adherence to the intervention and barriers to long term adherence, quality-of-life, fidelity of the implementation by CHWs, CHW's and study participants' acceptability and satisfaction with the intervention and eating behaviors. Placebo or tirzepatide will be injected subcutaneously in the abdomen or thigh once a week for 12 months.

Official Title
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Effect of Tirzepatide Plus Intensive Lifestyle Therapy on Body Weight and Metabolic Health in Latinos With Obesity

Conditions
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Obesity, Metabolic Disease

Intervention / Treatment
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* Behavioral: Standard Care
* Behavioral: Culturally-tailored dietary and behavioral intensive lifestyle intervention
* Drug: Placebo
* Drug: Tirzepatide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Self-reported Hispanic and/or Latino heritage Body Mass Index (BMI) 30-42 kg/m² HbA1c ≤ 6.4% Exclusion Criteria: Previous diagnosis of diabetes or fasting glucose ≥ 126 mg/dl or 2 hr oral glucose tolerance test plasma glucose ≥ 200 mg/dl Unstable weight (≥4% during the last 2 months prior to study enrollment) CPAP treatment for obstructive sleep apnea Severe cardiovascular disease within the 6 months prior to study enrollment Severe organ system dysfunction Known clinically significant gastric emptying abnormality History of chronic or acute pancreatitis Thyroid-stimulating hormone (TSH) >1.5X the upper limit of normal Medical conditions that cause obesity History of significantly active or unstable Major Depressive Disorder or other severe psychiatric disorder within the last 2 months Active substance abuse with alcohol or drugs Uncontrolled hypertension Liver disease Calcitonin level of ≥20 ng/L if eGFR ≥60 mL/min/1.73 m2 or ≥35 ng/L if eGFR <60 mL/min/1.73 m2 Family or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 History of active or untreated malignancy or are in remission from a clinically significant malignancy (other than basal- or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) for less than 5 years Severe anemia Pregnant or breastfeeding Metal implants that preclude MRI testing Use of medications that are known to affect the study outcome measures Do not agree to use contraception throughout the study period in male and female participants of reproductive and childbearing age Persons who are not able to grant voluntary informed consent Unable or unwilling to follow the study protocol Have any other condition not listed in this section (e.g. hypersensitivity or intolerance) that is a contraindication of GLP-1R agonists

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard Care<br>In this arm, participants will receive the standard care intervention from community health workers. | Behavioral: Standard Care<br>* Participants will meet with community health workers to receive general health information through individual check-ins.<br>|
| Experimental: Intensive lifestyle intervention plus placebo<br>In this arm, participants will receive a culturally-tailored dietary and behavioral intensive lifestyle intervention from community health workers, and will receive placebo subcutaneous injections weekly during the 52-week intervention. | Behavioral: Culturally-tailored dietary and behavioral intensive lifestyle intervention<br>* Participants will meet with community health workers to receive information focused on healthy eating while still adhering to a culturally-tailored plant-forward diet.<br>Drug: Placebo<br>* Participants will receive placebo subcutaneous injections.<br>|
| Experimental: Intensive lifestyle intervention plus tirzepatide<br>In this arm, participants will receive the behavioral plant-based intervention from community health workers, and will receive subcutaneous injections of tirzepatide weekly during the 52-week intervention | Behavioral: Culturally-tailored dietary and behavioral intensive lifestyle intervention<br>* Participants will meet with community health workers to receive information focused on healthy eating while still adhering to a culturally-tailored plant-forward diet.<br>Drug: Tirzepatide<br>* Participants will receive subcutaneous injections of tirzepatide that gradually increase up to 15 mg per week.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in body weight | Percent change in body weight | After 24 weeks of intervention | 
| Change in body weight | Percent change in body weight | After 52 weeks of intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants losing at least 5% in body weight | Proportion of participants in each group that lose at least 5% in body weight | After 24 weeks of intervention | 
| Proportion of participants losing at least 5% in body weight | Proportion of participants in each group that lose at least 5% in body weight | After 52 weeks of intervention | 
| Proportion of participants losing at least 10% in body weight | Proportion of participants in each group that lose at least 10% in body weight | After 24 weeks of intervention | 
| Proportion of participants losing at least 10% in body weight | Proportion of participants in each group that lose at least 10% in body weight | After 52 weeks of intervention | 
| Proportion of participants losing at least 15% in body weight | Proportion of participants in each group that lose at least 15% in body weight | After 24 weeks of intervention | 
| Proportion of participants losing at least 15% in body weight | Proportion of participants in each group that lose at least 15% in body weight | After 52 weeks of intervention | 
| Fat mass and fat free mass | Fat mass and fat free mass will be assessed using dual-energy x-ray absorptiometry (DXA) | Before and after 24 weeks of intervention | 
| Fat mass and fat free mass | Fat mass and fat free mass will be assessed using dual-energy x-ray absorptiometry (DXA) | Before and after 52 weeks of intervention | 
| β-cell function | β-cell function will be assessed from a modified 3-hour oral glucose tolerance test | Before and after 24 weeks of intervention | 
| β-cell function | β-cell function will be assessed from a modified 3-hour oral glucose tolerance test | Before and after 52 weeks of intervention | 
| Insulin clearance | Insulin clearance will be assessed from a modified 3-hour oral glucose tolerance test | Before and after 24 weeks of intervention | 
| Insulin clearance | Insulin clearance will be assessed from a modified 3-hour oral glucose tolerance test | Before and after 52 weeks of intervention | 
| Plasma lipids | Fasting plasma lipid profile will be assessed by routine blood tests | Before and after 24 weeks of intervention | 
| Plasma lipids | Fasting plasma lipid profile will be assessed by routine blood tests | Before and after 52 weeks of intervention | 
| Blood pressure | Systolic and diastolic blood pressure will be measured | Before and after 24 weeks of intervention | 
| Blood pressure | Systolic and diastolic blood pressure will be measured | Before and after 52 weeks of intervention | 
| Sleep quality | Sleep quality will be assessed by polysomnography. | Before and after 24 weeks of intervention | 
| Sleep quality | Sleep quality will be assessed by polysomnography. | Before and after 52 weeks of intervention | 
| Sleep quantity | Sleep quantity will be assessed by polysomnography. | Before and after 24 weeks of intervention | 
| Sleep quantity | Sleep quantity will be assessed by polysomnography. | Before and after 52 weeks of intervention | 
| Liver fat | Liver fat will be assessed by using ultrasound | Before and after 24 weeks of intervention | 
| Liver fat | Liver fat will be assessed by using ultrasound | Before and after 52 weeks of intervention | 
| Intra-abdominal fat mass and intrahepatic triglyceride content | Intra-abdominal fat mass and intrahepatic triglyceride content will be assessed via magnetic resonance imaging (MRI) | Before and after 52 weeks of intervention | 
| Physical performance | Physical performance will be measured as the time in seconds that takes to walk 50 ft and to stand up 5 times from a chair. | Before and after 24 weeks of intervention | 
| Physical performance | Physical performance will be measured as the time in seconds that takes to walk 50 ft and to stand up 5 times from a chair. | Before and after 52 weeks of intervention | 
| Grip strength | Grip strength will be measured using a hand dynamometer. | Before and after 24 weeks of intervention | 
| Grip strength | Grip strength will be measured using a hand dynamometer. | Before and after 52 weeks of intervention | 
| Lifestyle program adherence | Number of sessions attended | After 24 weeks of intervention | 
| Lifestyle program adherence | Number of sessions attended | After 52 weeks of intervention | 
| Drug/placebo adherence | Number of injections received | After 24 weeks of intervention | 
| Drug/placebo adherence | Number of injections received | After 52 weeks of intervention | 
| Program acceptability from community health workers and study participants | Community health workers' and study participants' perceptions of program acceptability via questionnaire | After 24 weeks of intervention | 
| Program acceptability from community health workers and study participants | Community health workers' and study participants' perceptions of program acceptability via questionnaire | After 52 weeks of intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Latinos, Obesity, Plant-forward diet, Tirzepatide