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

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

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.

Study Overview

• Status: Completed
• Conditions: Pseudohypoparathyroidism Type 1a; Albright Hereditary Osteodystrophy
• Intervention / Treatment: Drug: Theophylline

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 Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Unversity

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Theophylline; Patients will receive a 24 hour continuous infusion of intravenous theophylline.	Drug: Theophylline; 24 hour infusion of IV theophylline; Other Names: Theo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: Massachusetts General Hospital
• Investigators: Principal Investigator: Ashley H Shoemaker, MD, MSCI, Vanderbilt University

Publications and helpful links

General Publications

• Landreth H, Malow BA, Shoemaker AH. Increased Prevalence of Sleep Apnea in Children with Pseudohypoparathyroidism Type 1a. Horm Res Paediatr. 2015;84(1):1-5. doi: 10.1159/000381452. Epub 2015 Apr 23.
• Shoemaker AH, Lomenick JP, Saville BR, Wang W, Buchowski MS, Cone RD. Energy expenditure in obese children with pseudohypoparathyroidism type 1a. Int J Obes (Lond). 2013 Aug;37(8):1147-53. doi: 10.1038/ijo.2012.200. Epub 2012 Dec 11.

Helpful Links

• Vanderbilt PHP Research Page

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: May 20, 2015
• First Submitted That Met QC Criteria: June 2, 2015
• First Posted (Estimate): June 4, 2015

Study Record Updates

• Last Update Posted (Actual): June 26, 2017
• Last Update Submitted That Met QC Criteria: May 30, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Musculoskeletal Diseases; Bone Diseases; Metabolism, Inborn Errors; Bone Diseases, Metabolic; Calcium Metabolism Disorders; Metal Metabolism, Inborn Errors; Pseudohypoparathyroidism; Pseudopseudohypoparathyroidism; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Purinergic Antagonists; Purinergic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Theophylline
• Other Study ID Numbers: IRB 150497

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Investigators may contact Dr. Shoemaker for data after our primary analysis is completed and published (if applicable).