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

• Sponsor: Vanderbilt University Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02463409
• Collaborator: Massachusetts General Hospital (Other)
• Enrollment: 6
• Location: 1
• Arm: 1
• Duration (Months): 16
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pseudohypoparathyroidism Type 1a; Albright Hereditary Osteodystrophy	Drug: Theophylline	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effects of Theophylline on cAMP Signaling in Children With Pseudohypoparathyroidism Type 1a
• Study Start Date: Jun 1, 2015
• Actual Primary Completion Date: Oct 1, 2016
• Actual Study Completion Date: Oct 1, 2016

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change in Urine cAMP [1 day]

   Change in urine cAMP (after parathyroid hormone stimulation) before and during treatment with theophylline

Secondary Outcome Measures

1. Change in Resting Energy Expenditure (REE) [1 day]

   Change in REE before and during treatment with theophylline

2. Change in Apnea Hypopnea Index (AHI) [1 day]

   Change in AHI before and during treatment with theophylline

Eligibility Criteria

Criteria

• Ages Eligible for Study: 10 Years to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Vanderbilt Unversity	Nashville	Tennessee	United States	37232

Sponsors and Collaborators

• Vanderbilt University Medical Center
• Massachusetts General Hospital

Investigators

• Principal Investigator: Ashley H Shoemaker, MD, MSCI, Vanderbilt University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Vanderbilt PHP Research Page

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.

• Responsible Party: Ashley Shoemaker, Assistant Professor, Vanderbilt University Medical Center
• ClinicalTrials.gov Identifier: NCT02463409
• Other Study ID Numbers: IRB 150497
• First Posted: Jun 4, 2015
• Last Update Posted: Jun 26, 2017
• Last Verified: May 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Pseudohypoparathyroidism; Pseudopseudohypoparathyroidism; Theophylline

Study Results

Participant Flow

Pre-assignment Detail	The screening visit included labs, physical exam and medical history, prior to assignment to the theophylline arm.

Arm/Group Title	Theophylline
Arm/Group Description	Patients will receive a 24 hour continuous infusion of intravenous theophylline. Theophylline: 24 hour infusion of IV theophylline
Period Title: Overall Study
STARTED	6
COMPLETED	4
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Theophylline
Arm/Group Description	Patients will receive a 24 hour continuous infusion of intravenous theophylline. Theophylline: 24 hour infusion of IV theophylline
Overall Participants	5
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	14.4 (3.1)
Sex: Female, Male (Count of Participants)
Female	5 100%
Male	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	5 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	5 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Patients treated with theophylline who maintained appropriate IV access. Only 3 patients had complete data available.

Arm/Group Title	Theophylline
Arm/Group Description	Patients will receive a 24 hour continuous infusion of intravenous theophylline. Theophylline: 24 hour infusion of IV theophylline
Measure Participants	3
Mean (Standard Deviation) [fm/uL]	3048 (8369)

2. Secondary Outcome

Title	Change in Resting Energy Expenditure (REE)
Description	Change in REE before and during treatment with theophylline
Time Frame	1 day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Theophylline
Arm/Group Description	Patients will receive a 24 hour continuous infusion of intravenous theophylline. Theophylline: 24 hour infusion of IV theophylline
Measure Participants	4
Mean (Standard Error) [kcals per day]	-14 (68)

3. Secondary Outcome

Title	Change in Apnea Hypopnea Index (AHI)
Description	Change in AHI before and during treatment with theophylline
Time Frame	1 day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Theophylline
Arm/Group Description	Patients will receive a 24 hour continuous infusion of intravenous theophylline. Theophylline: 24 hour infusion of IV theophylline
Measure Participants	4
Mean (Standard Error) [units on a scale]	-0.60 (0.67)

Adverse Events

Time Frame	3 days
Adverse Event Reporting Description	We specifically asked patients about headache, nausea and vomiting at least twice daily. They were monitored continuously via telemetry for arrhythmia. Other adverse events were reported as described by the partiicipant.
Arm/Group Title	Theophylline
Arm/Group Description	Patients will receive a 24 hour continuous infusion of intravenous theophylline. Theophylline: 24 hour infusion of IV theophylline. All patients who enrolled in the study are included in this group (excluding screen fails).
All Cause Mortality
	Theophylline
	Affected / at Risk (%)	# Events
Total	0/5 (0%)
Serious Adverse Events
	Theophylline
	Affected / at Risk (%)	# Events
Total	0/5 (0%)
Other (Not Including Serious) Adverse Events
	Theophylline
	Affected / at Risk (%)	# Events
Total	4/5 (80%)
Cardiac disorders
Tachycardia	1/5 (20%)	1
Gastrointestinal disorders
Nausea	3/5 (60%)	3
Abdominal pain	1/5 (20%)	1
Vomiting	1/5 (20%)	1
Nervous system disorders
Headache	3/5 (60%)	3
dizziness	1/5 (20%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.