Theophylline treatment for a genetic disorder causing obesity and short stature

Phase 2 Study of Theophylline Treatment for Pseudohypoparathyroidism

This study is testing if theophylline can help children and young adults with a rare genetic disorder that causes obesity and short stature by improving their glucose levels and slowing down their growth.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 34 (estimated)
• Ages: 13 Years to 99 Years
• Sex: All
• Sponsor: Vanderbilt University Medical Center (Academic / other)
• Locations: 1 site (Nashville, Tennessee)
• Trial ID: NCT03029429 on ClinicalTrials.gov

What this trial studies

This phase 2 clinical trial investigates the efficacy of theophylline, a phosphodiesterase inhibitor, in treating pseudohypoparathyroidism, a rare genetic disorder characterized by early-onset obesity and short stature. The study aims to improve glucose tolerance, reduce body mass index (BMI), and slow growth plate closure in affected children and young adults. Participants will receive either theophylline or a placebo, and the outcomes will be measured to assess the drug's effectiveness in addressing the disorder's symptoms. The trial is designed to provide insights into a potential new treatment option for this condition.

Who should consider this trial

Good fit: Ideal candidates for this study are individuals aged 13 years and older with a clinical diagnosis of pseudohypoparathyroidism and obesity.

Not a fit: Patients with a history of certain medical conditions, such as cardiac arrhythmias or hepatic insufficiency, may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve weight management and metabolic health in patients with pseudohypoparathyroidism.

How similar studies have performed: While there is limited research on theophylline for this specific condition, the approach of using phosphodiesterase inhibitors has shown promise in other contexts.

Eligibility criteria

Inclusion Criteria:

1. Age 13 years and above
2. Clinical diagnosis of PHP (per the EuroPHP network classification guidelines1): Presence of PTH resistance or ectopic classification OR brachydactyly type E plus 2 minor criteria (TSH resistance, other hormonal resistance, developmental delay, intrauterine or post-natal growth retardation, obesity/overweight, specific facial features)
3. Obesity (BMI \>95th percentile for age/gender and/or ≥30 kg/m2)

Exclusion Criteria:

1. Use of a PDE inhibitor in the past 30 days
2. History of a seizure disorder unrelated to hypocalcemia
3. History of a cardiac arrhythmia (not including bradycardia)
4. Hepatic insufficiency including cirrhosis and acute hepatitis (AST or ALT \>3x upper limit of normal)
5. Congestive heart failure
6. Current cigarette use or alcohol abuse
7. Pregnancy or intention to become pregnant during the next year
8. Untreated hypothyroidism (defined as free thyroxine below the lower limit of normal)
9. Active peptic ulcer disease
10. Current use of medications known to effect theophylline levels
11. History of hypersensitivity to theophylline or other medication components
12. History of Major Depressive Disorder in the past 2 years, lifetime history of suicide attempt, history of any suicidal behavior in the past month, history of other sever psychiatric disorders (e.g. schizophrenia, bipolar disorder)
13. PHQ-9 score is ≥15 or suicidal ideation of type 4 or 5 (C-SSR) in the past month
14. Unable to comply with study procedures in the opinion of the investigator

Where this trial is running

Nashville, Tennessee

• Ashley Shoemaker — Nashville, Tennessee, United States (Recruiting)

Study contacts

• Principal investigator: Ashley Shoemaker, MD — Vanderbilt University Medical Center
• Study coordinator: Jenny Leshko, RN

Conditions Pseudohypoparathyroidism; Albright Hereditary Osteodystrophy; pseudohypoparathyroidism; AHO