Theophylline treatment for children with pseudohypoparathyroidism

Phase 2 Study of Theophylline Treatment for Pseudohypoparathyroidism

This study is testing if theophylline can help children with pseudohypoparathyroidism manage their weight and growth issues better than a placebo.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 34 (estimated)
• Ages: 2 Years to 12 Years
• Sex: All
• Sponsor: Vanderbilt University Medical Center (Academic / other)
• Locations: 1 site (Nashville, Tennessee)
• Trial ID: NCT04551170 on ClinicalTrials.gov

What this trial studies

This phase 2 clinical trial aims to evaluate the efficacy of theophylline, a phosphodiesterase inhibitor, in treating children aged 2 to 12 years with pseudohypoparathyroidism. The study hypothesizes that theophylline will help reduce body mass index (BMI), slow the rate of growth plate closure, and decrease hormone resistance associated with this genetic disorder. Participants will receive either theophylline or a placebo, and the trial will monitor changes in weight, growth, and hormone levels over time. The goal is to provide a new therapeutic approach for managing the symptoms of this rare condition.

Who should consider this trial

Good fit: Ideal candidates are children aged 2 to 12 years 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 growth outcomes for children with pseudohypoparathyroidism.

How similar studies have performed: While there is limited research on theophylline for this specific condition, PDE inhibitors have shown promise in other contexts, making this approach potentially novel.

Eligibility criteria

Inclusion Criteria:

* Age 2 to 12 years old
* Clinical diagnosis of PHP (per the EuroPHP network classification guidelines5): Presence of PTH resistance and/or ectopic ossification 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)
* 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 (see protection of human subjects)
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. Untreated hypothyroidism or uncontrolled PTH resistance (PTH \>2x upper limit of normal), or treatment of these disorders by medications other than calcitriol or levothyroxine (such as Cytomel or Armour thyroid)
15. Unable to comply with study procedures in the opinion of the investigator

Where this trial is running

Nashville, Tennessee

• Vanderbilt University Medical Center — 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 Type 1a; PHP; AHO