Clinical Trials Logo

Clinical Trial Summary

Pseudohypoparathyroidism is a genetic disorder with limited treatment options, characterized by early-onset obesity, short stature and resistance to multiple hormones. This phase 2 clinical trial and open-label extension study will test the efficacy of theophylline, a phosphodiesterase inhibitor, in pseudohypoparathyroidism. We hypothesize that theophylline will cause weight loss, slow the rate of growth plate closure and decrease hormone resistance in children.

Clinical Trial Description

Pseudohypoparathyroidism (PHP) is a rare, genetic disorder caused by impaired stimulatory G protein (Gsα) signaling through downregulation of the gene, GNAS. The resultant hormone abnormalities can be treated with hormone replacement therapy, but other aspects of the disorder such as early-onset obesity and short stature are without effective treatment options. Gsα signaling is essential for the normal hormonal function of the pituitary, thyroid, gonads, renal proximal tubules and hypothalamus. While many of the resulting hormone deficiencies can be treated with hormone replacement therapy (HRT), HRT is not an effective therapy for the severe early-onset obesity and short stature which are major features of the PHP phenotype. Therefore, the goal of this clinical trial is to test the efficacy of upstream therapy aimed at correcting the function of Gsα-dependent receptors in children with PHP. Gsα-coupled receptor signaling cascade begins with an increase in cyclic adenosine monophosphate (cAMP) which is rapidly degraded by the enzyme phosphodiesterase (PDE). PDE inhibitors act by prolonging cAMP signaling by decreasing the rate of degradation. Given that patients with PHP have reduced, but not completely absent, cAMP production, the investigators seek to test the hypothesis that the PDE inhibitor theophylline will reduce body mass index (BMI), slow the rate of epiphyseal closure, and decrease hormone resistance in children with PHP through improved Gsα-coupled receptor signaling. The investigators will conduct a 52-week randomized, placebo-controlled clinical trial of theophylline in children with PHP. Theophylline is a non-selective PDE inhibitor that is generically available and has a long history of use in pediatric patients, making it an ideal drug for repurposing in youth with PHP. Furthermore, the pharmacokinetics of theophylline are well understood, and serum drug levels are easily measured. Our primary outcome is change in BMI. Secondary outcome measures include change in epiphyseal closure and HRT medication doses. ;

Study Design

Related Conditions & MeSH terms

NCT number NCT04551170
Study type Interventional
Source Vanderbilt University Medical Center
Contact Jenny Leshko, RN
Phone 6153438116
Status Recruiting
Phase Phase 2
Start date July 13, 2020
Completion date June 30, 2026

See also
  Status Clinical Trial Phase
Recruiting NCT03029429 - Theophylline Treatment for Pseudohypoparathyroidism Phase 2
Recruiting NCT04969926 - Natural History Study of Parathyroid Disorders
Enrolling by invitation NCT04240821 - Theophylline for Treatment of Pseudohypoparathyroidism Phase 2
Completed NCT00004661 - Study of the Regulation of Parathyroid Hormone Secretion in Pseudohypoparathyroidism N/A
Recruiting NCT05945576 - IDMet (RaDiCo Cohort) (RaDiCo-IDMet)
Active, not recruiting NCT02551120 - Characterization of Patients With Non-surgical Hypoparathyroidism and Pseudohypoparathyroidism
Completed NCT02411461 - Early-onset Obesity and Cognitive Impairment in Children With Pseudohypoparathyroidism
Completed NCT00001242 - Studies of States With Resistance to Vitamin D and Parathyroid Hormone
Active, not recruiting NCT00497484 - Evaluation of rhGH Replacement Therapy in Patients With Pseudohypoparathyroidism Type Ia (PHP Ia) N/A