Albright Hereditary Osteodystrophy, Pseudohypoparathyroidism Type 1a
Conditions
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.
Interventions
DRUGTheophylline
24 hour infusion of IV theophylline
Sponsors
Massachusetts General Hospital
Vanderbilt University Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
10 Years to 21 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Urine cAMP | 1 day | Change in urine cAMP (after parathyroid hormone stimulation) before and during treatment with theophylline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Resting Energy Expenditure (REE) | 1 day | Change in REE before and during treatment with theophylline |
| Change in Apnea Hypopnea Index (AHI) | 1 day | Change in AHI before and during treatment with theophylline |
Countries
United States
Participant flow
Pre-assignment details
The screening visit included labs, physical exam and medical history, prior to assignment to the theophylline arm.
Participants by arm
| Arm | Count |
|---|---|
| Theophylline Patients will receive a 24 hour continuous infusion of intravenous theophylline.
Theophylline: 24 hour infusion of IV theophylline | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Screen failure | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Theophylline |
|---|---|
| Age, Continuous | 14.4 years STANDARD_DEVIATION 3.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Region of Enrollment United States | 5 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 5 |
| other Total, other adverse events | 4 / 5 |
| serious Total, serious adverse events | 0 / 5 |
Outcome results
Primary
Change in Urine cAMP
Change in urine cAMP (after parathyroid hormone stimulation) before and during treatment with theophylline
Time frame: 1 day
Population: Patients treated with theophylline who maintained appropriate IV access. Only 3 patients had complete data available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Theophylline | Change in Urine cAMP | 3048 fm/uL | Standard Deviation 8369 |
Secondary
Change in Apnea Hypopnea Index (AHI)
Change in AHI before and during treatment with theophylline
Time frame: 1 day
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Theophylline | Change in Apnea Hypopnea Index (AHI) | -0.60 units on a scale | Standard Error 0.67 |
Secondary
Change in Resting Energy Expenditure (REE)
Change in REE before and during treatment with theophylline
Time frame: 1 day
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Theophylline | Change in Resting Energy Expenditure (REE) | -14 kcals per day | Standard Error 68 |