Albright Hereditary Osteodystrophy: Natural History, Growth, and Cognitive/Behavioral Assessments

Connecticut Children's Medical Center

Status: Enrolling

Conditions: Pseudopseudohypoparathyroidism; Albright Hereditary Osteodystrophy; Pseudohypoparathyroidism Type 1A

Treatments: Behavioral: Neurocognitive and psychosocial testing

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00209235

R21HD078864 (U.S. NIH Grant/Contract)

16-110

Details and patient eligibility

About

We, the researchers, are following the natural history of Albright hereditary osteodystrophy. We 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 (under R01 FD002568, IND 67148, which ended); those who are growth hormone sufficient and were found to have a positive clinical response to growth hormone in a prior clinical trial (under R01 FD00FD003409, IND 67148, which ended); or those 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 (which has ended)

Full description

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 final adult height. 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 completed a study in which we treated 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. Some of these patients remain on growth hormone as per clinical care secondary to their responses.

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. AHO includes two subtypes: pseudohypoparathyroidism type 1A (PHP1A) and pseudopseudohypoparathyroidism (PPHP).

Enrollment: 600 estimated patients

Sex: All

Ages: 2 months to 89 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria for GH study:

• Diagnosis of pseudohypoparathyroidism type 1A with mutation confirmation
• For the portion of the study in which growth hormone is used for participants who are not growth hormone deficient (ie., growth hormone sufficient), the participant must be over 3 years of age (ie., after 3rd birthday) AND also be pre-pubertal at the time of GH initiation.
• As of now, the growth hormone sufficient participants must meet the FDA-approved criteria for idiopathic short stature or the SGA indication.

Therefore, for all participants enrolling in the growth hormone portion of this study as of now, the growth hormone is used according to FDA-approved indications, and growth hormone use is according to standard of care clinical guidelines.

Exclusion:

• Absence of above diagnosis and failure to meet above criteria

Inclusion Criteria for cognitive/behavioral studies:

• Confirmed diagnosis of Pseudohypoparathyroidism type 1A and Pseudopseudohypoparathyroidism with mutation confirmation
• Ages 4 - 65 yrs

Exclusion:

• Absence of above

Inclusion Criteria for Natural History Study:

• Confirmed diagnosis of Pseudohypoparathyroidism type 1A or Pseudopseudohypoparathyroidism with mutation confirmation
• Ages 0.2 yrs - 89 yrs

Exclusion:

• Absence of above

Trial design

Primary purpose: Other

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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600 participants in 1 patient group

AHO:neurocognitive and pyschosocial

Experimental group

Description:

Neurocognitive and psychosocial testing

Treatment:

Behavioral: Neurocognitive and psychosocial testing