Tirzepatide for Weight Loss in Prader-Willi Syndrome and Obesity

Recruiting at 2 trial locations

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: Grace Kim

Must not be taking: Weight loss drugs, Insulin, GLP1A, DPP4

Disqualifiers: Pregnancy, Pancreatitis, Diabetes, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: 48 weeks

36 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires that you stop taking any weight loss medications, insulin, sulfonylureas, or medications affecting insulin secretion or GLP1 clearance at least 3 months before starting the study. You also need to avoid any medications that might affect the study's results.

What data supports the effectiveness of the drug Tirzepatide for weight loss in Prader-Willi Syndrome and obesity?

While there is no direct data on Tirzepatide for Prader-Willi Syndrome, similar drugs like GLP-1 agonists have shown significant weight loss in individuals with this condition. For example, a patient with Prader-Willi Syndrome lost 125 lbs using GLP-1 agonists, suggesting potential effectiveness of similar treatments. ^{1 2 3 4 5}

Is tirzepatide safe for humans?

Tirzepatide has been shown to be generally safe in humans, with the most common side effects being mild to moderate stomach-related issues like nausea, vomiting, and diarrhea. These side effects are similar to those seen with other medications in the same class and are usually temporary. ^{6 7 8 9 10}

How is the drug Tirzepatide unique for treating obesity in Prader-Willi Syndrome?

Tirzepatide is unique because it combines the effects of GLP-1 agonists, which have shown success in weight loss for Prader-Willi Syndrome, with additional mechanisms that may enhance its effectiveness. This dual action could potentially offer more significant weight management benefits compared to existing treatments. ^{1 2 3 11 12}

Eligibility Criteria

This trial is for young adults with Prader-Willi Syndrome, hypothalamic obesity, or general obesity without a genetic syndrome. Participants will be given Tirzepatide for weight loss over a year to see its effects on weight and health.

Inclusion Criteria

Consistent caregiver if 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 to prevent unintentional pregnancy during the study

Exclusion Criteria

I am currently using or have recently used weight loss medications.

Significant weight change (>3% weight gain or loss) in the last 2 months prior to enrollment

Current pregnancy, desire to become pregnant within study period, or current lactation

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tirzepatide for once-weekly dosing over 48 weeks, with regular monitoring and assessments

48 weeks

6 visits (in-person), 4 visits (virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Tirzepatide

Trial Overview The study tests the effectiveness of Tirzepatide, a weight loss medication, in different groups: those with Prader-Willi Syndrome/hypothalamic obesity versus those with non-syndromic obesity.

Participant Groups

Group I: General Non-Syndromic Obesity Active Control 1 Intervention

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.

Group II: Hypothalamic Obesity Active Control 1 Intervention

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.

Group III: Prader-Willi Syndrome Active Control 1 Intervention

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.

Who Is Running the Clinical Trial?

Grace Kim

Lead Sponsor

Trials

1

Recruited

40+

Vanderbilt University Medical Center

Collaborator

Trials

922

Recruited

939,000+

Seattle Children's Hospital

Collaborator

Trials

319

Recruited

5,232,000+

Children's Hospitals and Clinics of Minnesota

Collaborator

Trials

67

Recruited

5,022,000+

Findings from Research

A review of 14 studies and a case series of 10 adolescents with Prader-Willi syndrome (PWS) indicated that anti-obesity medications (AOMs) can help manage hyperphagia, with 60% of participants showing decreased or stable BMI z-scores after treatment.

No significant side effects were reported in the case series, suggesting that AOMs may be safe for use in youth with PWS, but further research is needed to establish comprehensive treatment guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-Obesity Medication Use in Children and Adolescents with Prader-Willi Syndrome: Case Review and Literature Search. Goldman, VE., Naguib, MN., Vidmar, AP.[2023]

In a 72-week phase 3 trial involving 938 adults with obesity and type 2 diabetes, tirzepatide (10 mg and 15 mg) led to significant weight loss, with reductions of -12.8% and -14.7% respectively, compared to only -3.2% with placebo.

The safety profile of tirzepatide was generally favorable, with most adverse events being mild to moderate gastrointestinal issues, and serious adverse events were rare, indicating it is a safe option for weight management in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Garvey, WT., Frias, JP., Jastreboff, AM., et al.[2023]

Tirzepatide, administered once weekly, was found to be effective in reducing obesity in individuals with type 2 diabetes, as demonstrated in a large phase 3 trial involving multiple centers.

The study was double-blind and placebo-controlled, ensuring robust results that support tirzepatide as a promising treatment option for weight management in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In adults with BMI ≥27 kg/m2 and type 2 diabetes, adding tirzepatide to a lifestyle intervention increased weight loss at 72 wk. Davidson, MB.[2023]

Tirzepatide, a novel GLP-1 receptor agonist, has been shown to significantly reduce A1C levels and body weight in patients with type 2 diabetes compared to placebo and other active treatments.

The safety profile of tirzepatide is similar to other GLP-1 receptor agonists, with the most common side effects being mild to moderate gastrointestinal issues, and it does not increase the risk of hypoglycemia, making it a promising treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Tirzepatide in Adults With Type 2 Diabetes: A Perspective for Primary Care Providers. Kushner, P., Anderson, JE., Simon, J., et al.[2023]

Tirzepatide, a new GLP-1 receptor agonist, was found to be more effective for weight loss compared to other GLP-1RAs like semaglutide and liraglutide, with significant weight loss observed in over 12,300 patients in the analysis.

While all GLP-1RAs were associated with gastrointestinal side effects, tirzepatide showed better efficacy outcomes for weight loss while maintaining a similar safety profile to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of glucagon-like peptide-1 receptor agonists for the management of obesity in adults without diabetes: A network meta-analysis of randomized clinical trials. Alkhezi, OS., Alahmed, AA., Alfayez, OM., et al.[2023]

In a systematic review of randomized controlled trials involving 5800 patients, tirzepatide was found to be highly effective for weight loss, with 78.22% achieving at least 5% weight loss and 32.28% achieving at least 15% weight loss.

Tirzepatide demonstrated superior weight loss compared to placebo and semaglutide, with a significant mean weight loss of -12.47 kg at the 5 mg dose, while showing a manageable safety profile with only a slight increase in gastrointestinal adverse events compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tirzepatide for treatment of overweight or obesity. A systematic review and meta-analysis. Tan, B., Pan, XH., Chew, HSJ., et al.[2023]

Exenatide, a GLP-1 agonist, was effectively used to manage diabetes in a 19-year-old female with Prader-Willi syndrome, highlighting its potential in this specific population.

The drug demonstrated beneficial effects in reducing weight and suppressing appetite, suggesting it could be a promising treatment strategy for obesity and diabetes associated with Prader-Willi syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating diabetes mellitus in Prader-Willi syndrome with Exenatide. Seetho, IW., Jones, G., Thomson, GA., et al.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Intensive management of obesity in people with Prader-Willi syndrome. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Anti-Obesity Medication Use in Children and Adolescents with Prader-Willi Syndrome: Case Review and Literature Search. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Weight Loss of Over 100 lbs in a Patient of Prader-Willi Syndrome Treated With Glucagon-Like Peptide-1 (GLP-1) Agonists. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Effects of MetAP2 inhibition on hyperphagia and body weight in Prader-Willi syndrome: A randomized, double-blind, placebo-controlled trial. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Effect of topiramate on eating behaviours in Prader-Willi syndrome: TOPRADER double-blind randomised placebo-controlled study. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

In adults with BMI ≥27 kg/m2 and type 2 diabetes, adding tirzepatide to a lifestyle intervention increased weight loss at 72 wk. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Tirzepatide in Adults With Type 2 Diabetes: A Perspective for Primary Care Providers. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of glucagon-like peptide-1 receptor agonists for the management of obesity in adults without diabetes: A network meta-analysis of randomized clinical trials. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tirzepatide for treatment of overweight or obesity. A systematic review and meta-analysis. [2023]

11. Ireland pubmed.ncbi.nlm.nih.gov

Treating diabetes mellitus in Prader-Willi syndrome with Exenatide. [2018]

12. United States pubmed.ncbi.nlm.nih.gov

Liraglutide for Weight Management in Children and Adolescents With Prader-Willi Syndrome and Obesity. [2023]