Theophylline for Treatment of Pseudohypoparathyroidism

Study Overview
=================
Brief Summary
-----------------
Pseudohypoparathyroidism is a genetic disorder with limited treatment options, characterized by early-onset obesity, short stature, hormone resistance and cognitive impairment. This phase 2 clinical trial will test the efficacy of theophylline, a phosphodiesterase inhibitor, in pseudohypoparathyroidism. We hypothesize that theophylline will cause weight loss, improve glucose tolerance and decrease hormone resistance in children and young adults.

Detailed Description
-----------------
Trial Objectives The primary objective of this study is to evaluate the long-term safety of theophylline in patients with PHP. The secondary objectives of this study are to evaluate changes in BMI, hormone resistance and epiphyseal closure associated with theophylline treatment of patients with PHP. Study Design The proposed study is a single center, 24-month open label extension clinical trial for patients with PHP who complete the randomized clinical trial.

Official Title
-----------------
Open-Label Extension Study of Theophylline for Treatment of Pseudohypoparathyroidism

Conditions
-----------------
Pseudohypoparathyroidism, Pseudohypoparathyroidism Type 1a, Albright Hereditary Osteodystrophy

Intervention / Treatment
-----------------
* Drug: Theophylline ER


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1. Successful completion of the randomized clinical trial Phase 2 Study of Theophylline Treatment of Pseudohypoparathyroidism IND 133103 (11/1/2016). Exclusion Criteria: History of a seizure disorder unrelated to hypocalcemia History of a cardiac arrhythmia (not including bradycardia) Hepatic insufficiency including cirrhosis and acute hepatitis (AST or ALT >3x upper limit of normal) Congestive heart failure Current cigarette use or alcohol abuse Pregnancy or intention to become pregnant during the next year Active peptic ulcer disease Current use of medications known to effect theophylline levels History of hypersensitivity to theophylline or other medication components Unable to comply with study procedures in the opinion of the investigator

Ages Eligible for Study
-----------------
Minimum Age: 2 Years
Maximum Age: 99 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This is an open-label extension study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open-label theophylline<br>Oral theophylline - either once daily capsule or q6h elixir. | Drug: Theophylline ER<br>* Oral theophylline<br>* Other names: Theophylline elixir;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Treatment-emergent adverse events will be compared before and during treatment | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BMI | Change in BMI | 24 months |