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

Albright Hereditary Osteodystrophy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02463409
• Other study ID #: IRB 150497
• Status: Completed
• Phase: Phase 2
• First received: May 20, 2015
• Last updated: January 17, 2017
• Start date: June 2015
• Est. completion date: October 2016

Study information

• Verified date: January 2017
• Source: Vanderbilt University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: October 2016
• Est. primary completion date: October 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 21 Years

Eligibility

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

Related Conditions & MeSH terms

• Albright Hereditary Osteodystrophy
• Pseudohypoparathyroidism
• Pseudohypoparathyroidism Type 1a

Intervention

Drug:
• Theophylline
24 hour infusion of IV theophylline

Locations

Country	Name	City	State
United States	Vanderbilt Unversity	Nashville	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
Vanderbilt University Medical Center	Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Urine cAMP	Change in urine cAMP (after parathyroid hormone stimulation) before and during treatment with theophylline	1 day
Secondary	Resting Energy Expenditure (REE)	Change in REE before and during treatment with theophylline	1 day
Secondary	Apnea Hypopnea Index (AHI)	Change in AHI before and during treatment with theophylline	1 day

External Links

•   Vanderbilt PHP Research Page