Tirzepatide in PWS, HO and GNSO

The Effects of Tirzepatide in Young Adults With Prader-Willi Syndrome, Hypothalamic Obesity and General Non-Syndromic Obesity

This research study is comparing the effectiveness of a weight loss medication called Tirzepatide in young adults with Prader-Willi Syndrome and/or hypothalamic obesity, as compared to young adults with obesity that is unrelated to a genetic syndrome or underlying medical cause. These groups will be given medication for 1 year to see how weight and other health factors are effected by the medication.

Study Overview

• Status: Recruiting
• Conditions: Prader-Willi Syndrome; Hypothalamic Obesity; Obesity/Therapy
• Intervention / Treatment: Drug: Tirzepatide

Detailed Description

This study is for the following individuals:

• Age 18-26.
• Have Prader-Willi Syndrome, Hypothalamic Obesity, or Obesity unrelated to a genetic syndrome or medical condition.
• Have a BMI in the obesity range

If you/your child decide to take part in the research study, you/your child would participate in the study for approximately 56-60 weeks. During this time the following can be expected:

• Receive tirzepatide for once-weekly dosing.
• Complete 6 in-person SCH study visits
• Complete 4 telehealth visits.

• Complete the following research procedures:

  • Medical Record Review
  • Vital Signs
  • Anthropometry (e.g., height, weight, waist measurements)
  • Physical Exams
  • Laboratory Tests (e.g., fasting blood draws, urine test)
  • Dual-Energy Absorptiometry (DXA) scans
  • Questionnaires

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Saint Paul, Minnesota, United States, 55102
      • Recruiting
      • Children's Minnesota
      • Principal Investigator: Jennifer Abuzzahab, MD
      • Contact: Diabetes/Endocrinology Research Team; Phone Number: 651-220-5730; Email: endocrineresearch@childrensmn.org
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Vanderbilt University Medical Center
      • Principal Investigator: Ashley Shoemaker, MD
      • Contact: Martha Upchurch; Phone Number: 6158754274; Email: martha.upchurch@vumc.org
  • Washington
    • Seattle, Washington, United States, 98105
      • Recruiting
      • Seattle Children's Hospital
      • Contact: Endocrine Research Team; Phone Number: 206-987-2540; Email: EndocrineResearch@seattlechildrens.org
      • Principal Investigator: Grace Kim, MD
      • Sub-Investigator: Parisa Salehi, MD
      • Sub-Investigator: Melinda Pierce, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Individuals 18-26 years with a BMI in the obesity range (BMI ≥95th percentile for age and sex or ≥30 kg/m2) with either 1) genetically confirmed diagnosis of PWS, 2) hypothalamic obesity as defined by damage to the medial hypothalamic region resulting in dysregulation of satiety and energy balance as diagnosed by a physician, 3) general obesity unrelated to a genetic syndrome or underlying medical condition
• In a stable care setting at least 6 months prior to enrollment
• Able and willing to participate in study visits including tolerating blood draws, urine samples and tolerate DXA scan.
• Ability to take weekly subcutaneous tirzepatide
• Consistent caregiver if they are not independent
• Stable diet and exercise regimen for at least 6 months prior to enrollment
• Able to use contraceptive methods if able to conceive offspring in order to prevent unintentional pregnancy during the study

Exclusion Criteria:

• Current or recent (within 3 months of start of study drug initiation) use of weight loss medications
• Current use of insulin or sulfonylurea or other medication affecting insulin secretion or GLP1 clearance
• Current or prior use of any GLP1A or DPP4 inhibitor during the 6 months before screening
• Any medications that may affect the study endpoints
• Significant weight change (>3% weight gain or loss) in the last 2 months prior to enrollment
• Change in dose of chronic endocrine medications (testosterone, estrogen, levothyroxine, or growth hormone medications) >10%/kg/day for at least 3 months prior to study
• Current pregnancy or desire to become pregnant within study period, current lactation
• History of recurrent pancreatitis, CKD, gastroparesis
• Chronic/acute heart, kidney, or liver disease
• Personal or family history of medullary thyroid carcinoma or MEN syndrome type 2
• Uncontrolled diabetes (A1C >8.5%)
• DVT
• Cancer within the previous 5 years
• Current participation in an interventional clinical study
• Previous or planned surgical treatment for obesity
• Individuals with current substance abuse equivalnt to moderate or severe based on DSM 5 criteria (Hasin DS, 2013)
• Any suicidal ideation in the past year
• Unable to perform any of the procedures for the study
• Have a body weight, height, and/or width that that prohibits the ability to obtain accurate measurements according to the DXA manufacturer's specification
• Any condition that would prevent successful participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Prader-Willi Syndrome; Individuals 18-26 years with a BMI in the obesity range (BMI ≥95th percentile for age and sex or ≥30 kg/m2) with genetically confirmed Prader-Willi Syndrome between 18-26 years old.	Drug: Tirzepatide; Subjects will take Tirzepatide for 48 weeks
Active Comparator: Hypothalamic Obesity; Individuals 18-26 years with a BMI in the obesity range (BMI ≥95th percentile for age and sex or ≥30 kg/m2) and hypothalamic obesity as defined by damage to the medial hypothalamic region resulting in dysregulation of satiety and energy balance as diagnosed by a physician.	Drug: Tirzepatide; Subjects will take Tirzepatide for 48 weeks
Active Comparator: General Non-Syndromic Obesity; Individuals 18-26 years with a BMI in the obesity range (BMI ≥95th percentile for age and sex or ≥30 kg/m2) and general obesity unrelated to a genetic syndrome or underlying medical condition.	Drug: Tirzepatide; Subjects will take Tirzepatide for 48 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in weight	Weight will be measured in kilograms through anthropometric measurements. Change in percent weight from baseline to week 48 of treatment with tirzepatide in young adults with PWS, HO, GNSO and obesity will then be assessed.	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in BMI	Change in BMI from baseline to 48 weeks of treatment with tirzepatide in young adults with PWS, HO, GNSO and obesity through anthropometric measurements. BMI will be calculated using weight (kg) and height (m) which will be combined to report BMI in kg/m^2. The percent change in this BMI value from baseline to 48 weeks will be calculated.	48 weeks
Change in fat mass	Change in fat mass (measured in kg by DXA scan) from baseline to 48 weeks of treatment with tirzepatide in young adults with PWS, HO, GNSO and obesity.	48 weeks
Change in appetite - CoEQ (Control of Eating Questionnaire)	Change in appetite during 48 weeks of treatment with tirzepatide in young adults with PWS, HO, GNSO and obesity using an appetite questionnaire (CoEQ - Control of Eating Questionnaire). CoEQ is a 21-item scale to assess the severity and type of food cravings an individual experiences using a visual analog scale. Higher scores indicate higher severity of hyperphagia.	48 weeks
Change in appetite - Physician Rated Hyperphagia Severity Scale	Change in appetite during 48 weeks of treatment with tirzepatide in young adults with PWS, HO, GNSO and obesity assed with a physician rated hyperphagia severity scale. This is a 5 point scale (0 to 5) to rate clinical imppression of hyperphagia severity. Higher scores mean more severity.	48 weeks
Change in metabolic markers - fasting lipids	Change in metabolic markers during 48 weeks of treatment with tirzepatide in young adults with PWS, HO, GNSO and obesity including: fasting lipids via lipid profile assay via blood sample	48 weeks
Change in metabolic markers - fasting plasma glucose	Change in metabolic markers during 48 weeks of treatment with tirzepatide in young adults with PWS, HO, GNSO and obesity including: fasting plasma glucose, via chemistry panel via blood sample	48 weeks
Change in metabolic markers- fasting insulin	Change in metabolic markers during 48 weeks of treatment with tirzepatide in young adults with PWS, HO, GNSO and obesity including: fasting insulin via insulin assay via blood sample	48 weeks
Change in metabolic markers - hemoglobin A1C	Change in metabolic markers during 48 weeks of treatment with tirzepatide in young adults with PWS, HO, GNSO and obesity including: hemoglobin A1C via hemoglobin A1C assay via blood sample	48 weeks
Change in metabolic markers- Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)	Change in metabolic markers during 48 weeks of treatment with tirzepatide in young adults with PWS, HO, GNSO and obesity including: Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). This is product measuring insulin resistance calculated using fasting insulin and fasting glucose values. Higher numbers indicate more insulins resistance.	48 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in safety markers -CBC	Change in safety markers during 48 weeks of treatment with tirzepatide in young adults with PWS, HO, GNSO and obesity including: Complete Blood Count (CBC). This will be done with standard CBC assays via blood sample	48 weeks
Change in safety markers - CMP	Change in safety markers during 48 weeks of treatment with tirzepatide in young adults with PWS, HO, GNSO and obesity including: Comprehensive Metabolic Panel (CMP). This will be done with standard CMP assays via blood sample.	48 weeks
Change in safety markers - coagulation factor assay PT [prothrombin time]	Change in safety markers during 48 weeks of treatment with tirzepatide in young adults with PWS, HO, GNSO and obesity including: PT [prothrombin time], This assay will be done on drawn blood samples.	48 weeks
Change in safety markers - coagulation factor assay- PTT [Activated Partial Thromboplastin Time ]	Change in safety markers during 48 weeks of treatment with tirzepatide in young adults with PWS, HO, GNSO and obesity including: , PTT [Activated Partial Thromboplastin Time ].This assay will be done on drawn blood samples.	48 weeks
Change in safety markers - coagulation factor assay - INR [international normalized ratio].	Change in safety markers during 48 weeks of treatment with tirzepatide in young adults with PWS, HO, GNSO and obesity including: INR [international normalized ratio]. This assay will be done on drawn blood samples.	48 weeks

Collaborators and Investigators

• Sponsor: Grace Kim
• Collaborators: Seattle Children's Hospital; Vanderbilt University Medical Center; Children's Hospitals and Clinics of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: March 14, 2025
• First Submitted That Met QC Criteria: March 27, 2025
• First Posted (Actual): March 28, 2025

Study Record Updates

• Last Update Posted (Estimated): September 16, 2025
• Last Update Submitted That Met QC Criteria: September 12, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Obesity; Prader-Willi Syndrome; Tirzepatide; Hypothalamic Obesity; GLP1 Agonist; General Obesity
• Additional Relevant MeSH Terms: Urogenital Diseases; Imprinting Disorders; Neurologic Manifestations; Endocrine System Diseases; Nervous System Diseases; Nutrition Disorders; Male Urogenital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genetic Diseases, Inborn; Overnutrition; Body Weight; Neurobehavioral Manifestations; Gonadal Disorders; Congenital Abnormalities; Abnormalities, Multiple; Overweight; Intellectual Disability; Disorders of Sex Development; Urogenital Abnormalities; Chromosome Disorders; Gonadal Dysgenesis; Hypogonadism; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Prader-Willi Syndrome; Sexual Infantilism; Amino Acids, Peptides, and Proteins; Proteins; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide; Tirzepatide
• Other Study ID Numbers: STUDY00004995; I8F-NS-I001 (Other Grant/Funding Number: Lilly USA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes