Theophylline as a Treatment for Children With Pseudohypoparathyroidism Type 1a (Albright Hereditary Osteodystrophy)

Study Overview
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Brief Summary
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This study will test an investigational drug, theophylline, in children with pseudohypoparathyroidism type 1a (PHP1a). This study involves a 3 day visit to the Vanderbilt Clinical Research Center.

Detailed Description
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Study measures will be done at baseline and during a 24h infusion of IV theophylline. Theophylline levels will be drawn to ensure therapeutic dosing and to monitor for toxicity. Measures include laboratory values, response to PTH infusion and resting energy expenditure.

Official Title
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Effects of Theophylline on cAMP Signaling in Children With Pseudohypoparathyroidism Type 1a

Conditions
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Pseudohypoparathyroidism Type 1a, Albright Hereditary Osteodystrophy

Intervention / Treatment
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* Drug: Theophylline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 10 to 21 years old English proficiency Clinical and genetic diagnosis of PHP1a Exclusion Criteria: Use of a PDE inhibitor in the past 30 days History of a seizure disorder unrelated to hypocalcemia History of a cardiac arrhythmia (not including bradycardia) History of hepatic insufficiency AST or ALT >2x upper limit of normal Total bilirubin >1.5 x upper limit of normal (unless patient has a diagnosis of Gilbert's syndrome and no other causes leading to hyperbilirubinemia are identified) Congestive heart failure Cigarette use in the past 30 days Alcohol use within the past 24 hours Current pregnancy Untreated hypothyroidism (defined as free T4 level < 0.6 ng/dL or TSH >10 mcU/mL) Active peptic ulcer disease Fever >101 degrees in the past 24 hours Current use of medications known to effect theophylline levels (listed below) Severe sleep apnea requiring BiPAP Drugs with clinically significant drug interactions with theophylline: Allopurinol Cimetidine Ciprofloxacin Clarithromycin Enoxacin Ephedrine Erythromycin Estrogen Flurazepam Fluvoxamine Lithium Lorazepam Methotrexate Midazolam Pentoxifylline Propranolol Rifampin Sulfinpyrazone Tacrine Thiabendazole Ticlopidine Troleandomycin Verapamil

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Theophylline<br>Patients will receive a 24 hour continuous infusion of intravenous theophylline. | Drug: Theophylline<br>* 24 hour infusion of IV theophylline<br>* Other names: Theo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Urine cAMP | Change in urine cAMP (after parathyroid hormone stimulation) before and during treatment with theophylline | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Resting Energy Expenditure (REE) | Change in REE before and during treatment with theophylline | 1 day | 
| Change in Apnea Hypopnea Index (AHI) | Change in AHI before and during treatment with theophylline | 1 day |