Growth Hormone Use in Albright Hereditary Osteodystrophy

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
Sponsor:
Collaborator:
Johns Hopkins University
Information provided by (Responsible Party):
Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
ClinicalTrials.gov Identifier:
NCT00209235
First received: September 13, 2005
Last updated: February 27, 2014
Last verified: February 2014
  Purpose

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 (ie., growth hormone sufficient).

Funding source -- FDA OOPD [R01 FD003409 (in progress) and R01 FD002568 (which has ended)]


Condition Intervention Phase
Pseudohypoparathyroidism Type 1a
Albright Hereditary Osteodystrophy
Drug: Growth hormone
Drug: Growth Hormone
Phase 2
Phase 3

Study Type: Interventional
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 (Subtype of Albright Hereditary Osteodystrophy)

Resource links provided by NLM:


Further study details as provided by Hugo W. Moser Research Institute at Kennedy Krieger, Inc.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 200
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)
Arms Assigned Interventions
Growth hormone

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
Growth hormone
Other Names:
  • Nutropin AQ
  • Nutropin
  • Genotropin
  • Saizen
  • Norditropin
  • Humatrope
  • Tev-tropin
  • Omnitrope
Drug: Growth Hormone

Pseudohypoparathyroidism type 1a (growth hormone deficient): subcutaneous form, 0.15 mg -0.3 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.

Other Names:
  • Nutropin AQ
  • Nutropin
  • Genotropin
  • Saizen
  • Norditropin
  • Humatrope
  • Tev-tropin
  • Omnitrope

Detailed 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 and obesity, 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 (ie., 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.

  Eligibility

Ages Eligible for Study:   2 Months to 89 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of pseudohypoparathyroidism type 1a
  • 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 patient must be over 3 years of age (ie., after 3rd birthday) AND also be pre-pubertal at the time of GH initiation.

Exclusion Criteria:

  • Absence of above diagnosis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00209235

Contacts
Contact: Emily L Germain-Lee, MD 443-923-2703 germainlee@kennedykrieger.org

Locations
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    germainlee@kennedykrieger.org   
Principal Investigator: Emily L Germain-Lee, MD         
Sponsors and Collaborators
Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
Johns Hopkins University
Investigators
Principal Investigator: Emily L Germain-Lee, MD Kennedy Krieger Institute and Johns Hopkins University School of Medicine
  More Information

Additional Information:
Publications:
Long DN, Levine MA, Germain-Lee EL. Bone mineral density in patients with pseudohypoparathyroidism type 1a. EndoTrends 12(4):4,2006.
Crane JL, Shamblott MJ, Axelman J, Hsu S, Levine MA, Germain-Lee EL. Imprinting Status of G(alpha)s, NESP55, and XL(alpha)s in Cell Cultures Derived from Human Embryonic Germ Cells. Clinical and Translational Science,E-pub, 2 (5): 355-360, 2009.

Responsible Party: Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
ClinicalTrials.gov Identifier: NCT00209235     History of Changes
Other Study ID Numbers: NA_00044877, R01 FD003409, R01 FD002568
Study First Received: September 13, 2005
Last Updated: February 27, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Hugo W. Moser Research Institute at Kennedy Krieger, Inc.:
Pseudohypoparathyroidism Type 1a (PHP 1a)
Albright Hereditary Osteodystrophy
Growth Hormone Deficiency

Additional relevant MeSH terms:
Pseudohypoparathyroidism
Pseudopseudohypoparathyroidism
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Metal Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Calcium Metabolism Disorders
Metabolic Diseases
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 16, 2014