Theophylline Treatment for Pseudohypoparathyroidism - Children 2-12 Years Old

• Status: Recruiting
• Trial end date: 2025-06-30
• Target enrollment: 0
• Participant gender: All

Summary

Pseudohypoparathyroidism is a genetic disorder with limited treatment options, characterized by early-onset obesity, short stature and resistance to multiple hormones. This phase 2 clinical trial and open-label extension study will test the efficacy of theophylline, a phosphodiesterase inhibitor, in pseudohypoparathyroidism. We hypothesize that theophylline will cause weight loss, slow the rate of growth plate closure and decrease hormone resistance in children.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Vanderbilt University Medical Center
• Treatments: Theophylline

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