Albright Hereditary Osteodystrophy: Growth Hormone Trial and Cognitive/Behavioral Assessments
We, the researchers, have found that growth hormone deficiency is very common in patients with pseudohypoparathyroidism type 1a, which falls under the broader condition termed Albright hereditary osteodystrophy. Patients with pseudohypoparathyroidism type 1a typically are short and obese. Some of these patients are not short during childhood, but due to a combination of factors, they end up short as adults. We are evaluating the effect of growth hormone treatment in those patients with pseudohypoparathyroidism type 1a who are found to be growth hormone deficient. We hypothesize that growth hormone deficiency may contribute to the short stature and obesity found in this condition. We are also evaluating the effect of growth hormone on patients with pseudohypoparathyroidism type 1a who are not growth hormone deficient (i.e., growth hormone sufficient) in those who had been on study drug through R01 FD003409 or who meet the criteria of idiopathic short stature or SGA.
We are also evaluating neurocognitive and psychosocial functioning in participants with AHO in order to determine the specific impairments that are most common in the condition and to determine the best approach toward management.
Funding source -- Growth hormone study: FDA OOPD [R01 FD003409 (which has ended) and R01 FD002568 (which has ended)] Cognitive/behavior: NICHD R21 HD078864
Pseudohypoparathyroidism Type 1a
Albright Hereditary Osteodystrophy
Drug: Growth hormone
Drug: Growth Hormone
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Study of Growth Hormone Use in Patients With Pseudohypoparathyroidism Type 1a and Assessment of Cognitive/Behavioral Status in Albright Hereditary Osteodystrophy|
- PHP1a: Effect of GH on height, growth velocity, final height in children. Effect on weight, BMI, lipids, self-esteem in all ages. [ Time Frame: until achieve final height (approximately 12-15 years) ] [ Designated as safety issue: Yes ]
- Cognitive and behavioral function in Albright hereditary osteodystrophy [ Time Frame: participant will be assessed on day 1; assessment may extend into day 2 ] [ Designated as safety issue: No ]
|Study Start Date:||January 2003|
|Estimated Study Completion Date:||December 2025|
|Estimated Primary Completion Date:||October 2019 (Final data collection date for primary outcome measure)|
Growth hormone use in PHP1a.
For GH deficient PHP1a participants, the GH use is under FDA-approved indications, and the GH is considered as treatment (not study drug).
For GH sufficient PHP1a participants (all are children), the GH use is considered as study drug unless the patient meets the criteria of idiopathic short stature (in which case the GH is considered an FDA-approved treatment).
Drug: Growth hormone
Other Names:Drug: Growth Hormone
Pseudohypoparathyroidism type 1a (growth hormone deficient): subcutaneous form, 0.15 mg - 0.30 mg per kg per week divided into daily doses, titrated by response and IGF-1 levels. The duration is participant dependent.
For phase for growth hormone sufficient participants with PHP1a, dosage may be up to 0.37 mg per kg per week divided into daily doses subcutaneously, titrated by response and IGF-1 levels. The duration is participant dependent and also dependent on length of study and period of active recruitment.
For all GH-sufficient participants, the GH use is initiated in patients who are over 3 years of age and who are pre-pubertal provided that there are no contraindications to its use. [Enrollment for study drug has been completed and supply of study drug has ended.] As of now, the growth hormone sufficient participants must meet the criteria of idiopathic short stature or SGA indication in order to be considered for GH.
Pseudohypoparathyroidism type 1a (PHP1a) is a disorder that causes many endocrine and developmental problems. To date, medical treatment has focused primarily on maintenance of normal serum levels of calcium, phosphorous, and thyroid hormone. However, these therapeutic interventions do not address the problems of short stature, obesity, and subcutaneous ossifications, which for many are a source of considerable morbidity and personal distress. These patients require frequent medical care, blood tests, and medication adjustments. PHP1a is an inherited condition with an estimated prevalence in the United States of 1:15,000- 20,000, and the studies that we propose provide an opportunity to improve the quality of life in affected patients. We have found that growth hormone (GH) deficiency is common in these patients, and our data suggest that GH testing should be part of their routine standard of care. We are investigating whether GH treatment can increase linear growth velocity and final adult height in children. We are also investigating whether GH treatment can reduce weight and improve a variety of metabolic disturbances and overall health in both children and adults.
GH deficiency not only leads to short stature and obesity, but also to osteoporosis, hyperlipidemia, depressed cardiac and renal function, as well as an overall lack of energy. It is quite possible that treatment of GH-deficient patients with PHP1a could improve any or all of the above problems. GH treatment has been FDA approved for use in both children and adults with GH deficiency. Therefore, it may be possible to provide improvement in health and overall quality of life in these patients.
Additionally, we have initiated a research study for which we are treating children with PHP1a who are not GH deficient (i.e., GH sufficient). The rationale is that GH treatment could maximize linear growth velocity prior to the premature bone fusion that occurs in this condition and potentially improve final adult height. The supply of growth hormone has ended for this study, and we are following those participants who were in this study and received the growth hormone supply.
This study also seeks to define the specific neurocognitive and psychosocial disabilities in individuals with AHO in order to develop therapies and improve quality of life.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00209235
|Contact: Emily L Germain-Lee, MDfirstname.lastname@example.org|
|United States, Maryland|
|Kennedy Krieger Institute and Johns Hopkins Hospital||Recruiting|
|Baltimore, Maryland, United States, 21205|
|Contact: Emily L Germain-Lee, MD 443-923-2703 email@example.com|
|Principal Investigator: Emily L Germain-Lee, MD|
|Principal Investigator:||Emily L Germain-Lee, MD||Kennedy Krieger Institute and Johns Hopkins University School of Medicine|