Phase 2 Study of Theophylline Treatment for Pseudohypoparathyroidism

IND 133103

Pseudohypoparathyroidism is a genetic disorder with limited treatment options. Patients have early-onset obesity, short stature and increased risk of type 2 diabetes. This phase 2 clinical trial will test the efficacy of theophylline, a phosphodiesterase inhibitor, in pseudohypoparathyroidism. The investigators hypothesize that theophylline will cause weight loss, improve glucose tolerance and slow growth plate closure in children and young adults.

2018-09-01

2026-07-01

2026-11-01

Recruiting

Early phase I

34

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

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 34, 'type': 'ESTIMATED'}}

2024-04-02