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

Overview

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.

Full Title of Study: “Effects of Theophylline on cAMP Signaling in Children With Pseudohypoparathyroidism Type 1a”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: October 2016

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.

Interventions

  • Drug: Theophylline
    • 24 hour infusion of IV theophylline

Arms, Groups and Cohorts

  • Experimental: Theophylline
    • Patients will receive a 24 hour continuous infusion of intravenous theophylline.

Clinical Trial Outcome Measures

Primary Measures

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

Secondary Measures

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

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 10 Years

Maximum Age: 21 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Vanderbilt University Medical Center
  • Collaborator
    • Massachusetts General Hospital
  • Provider of Information About this Clinical Study
    • Principal Investigator: Ashley Shoemaker, Assistant Professor – Vanderbilt University Medical Center
  • Overall Official(s)
    • Ashley H Shoemaker, MD, MSCI, Principal Investigator, Vanderbilt University

References

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.

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