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

Phase 2

Completed

• Conditions: Pseudohypoparathyroidism Type 1a; Albright Hereditary Osteodystrophy
• Interventions: Drug: Theophylline

• Registration Number: NCT02463409
• Lead Sponsor: Vanderbilt University Medical Center

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2015-05-20
• Study Start: 2015-06
• Study First Submitted QC: 2015-06-02
• Study First Posted: 2015-06-04
• Primary Completion: 2016-10
• Study Completion: 2016-10
• Results First Submitted: 2017-04-19
• Results First Submitted QC: 2017-04-19
• Status Verified: 2017-05
• Results First Posted: 2017-05-30
• Last Update Submitted: 2017-05-30
• Last Update Posted: 2017-06-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 6

Inclusion Criteria

1. Age 10 to 21 years old
2. English proficiency
3. Clinical and genetic diagnosis of PHP1a

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. History of hepatic insufficiency
5. AST or ALT >2x upper limit of normal
6. 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)
7. Congestive heart failure
8. Cigarette use in the past 30 days
9. Alcohol use within the past 24 hours
10. Current pregnancy
11. Untreated hypothyroidism (defined as free T4 level < 0.6 ng/dL or TSH >10 mcU/mL)
12. Active peptic ulcer disease
13. Fever >101 degrees in the past 24 hours
14. Current use of medications known to effect theophylline levels (listed below)
15. 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Theophylline	Theophylline	Patients will receive a 24 hour continuous infusion of intravenous theophylline.

Primary Outcome Measures

Name	Time	Method
Change in Urine cAMP	1 day	Change in urine cAMP (after parathyroid hormone stimulation) before and during treatment with theophylline

Secondary Outcome Measures

Name	Time	Method
Change in Apnea Hypopnea Index (AHI)	1 day	Change in AHI before and during treatment with theophylline
Change in Resting Energy Expenditure (REE)	1 day	Change in REE before and during treatment with theophylline

Trial Locations

Locations (1)

Vanderbilt Unversity; 🇺🇸 Nashville, Tennessee, United States