NCT00209235

Brief Summary

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)

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
600

participants targeted

Target at P75+ for not_applicable

Timeline
56mo left

Started Jan 2003

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress84%
Jan 2003Dec 2030

Study Start

First participant enrolled

January 1, 2003

Completed
2.7 years until next milestone

First Submitted

Initial submission to the registry

September 13, 2005

Completed
8 days until next milestone

First Posted

Study publicly available on registry

September 21, 2005

Completed
25 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2030

Expected
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2030

Last Updated

May 28, 2025

Status Verified

May 1, 2025

Enrollment Period

27.8 years

First QC Date

September 13, 2005

Last Update Submit

May 23, 2025

Conditions

Pseudohypoparathyroidism Type 1AAlbright Hereditary OsteodystrophyPseudopseudohypoparathyroidism

Keywords

Pseudohypoparathyroidism Type 1A (PHP 1A)Albright Hereditary Osteodystrophy (AHO)Pseudopseudohypoparathyroidism (PPHP)Growth Hormone DeficiencyCognition and Behavior

Outcome Measures

Primary Outcomes (2)

  • PHP1A: Effect of GH on height, growth velocity, final height in children. Effect on weight, BMI, lipids, BMD, self-esteem in all ages.

    Effect of growth hormone

    until achieve final height (approximately 12-15 years)

  • Cognitive and behavioral function in Albright hereditary osteodystrophy

    Cognitive and behavioral function assessments/questionnaires

    participant will be assessed on day 1; assessment may extend into day 2

Study Arms (1)

AHO:neurocognitive and pyschosocial

EXPERIMENTAL

Neurocognitive and psychosocial testing

Behavioral: Neurocognitive and psychosocial testing

Interventions

Neurocognitive and psychosocial testingBEHAVIORAL

Neurocognitive and psychosocial testing

AHO:neurocognitive and pyschosocial

Eligibility Criteria

Age2 Months - 89 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • Absence of above diagnosis and failure to meet above criteria
  • Confirmed diagnosis of Pseudohypoparathyroidism type 1A and Pseudopseudohypoparathyroidism with mutation confirmation
  • Ages 4 - 65 yrs
  • Absence of above
  • Confirmed diagnosis of Pseudohypoparathyroidism type 1A or Pseudopseudohypoparathyroidism with mutation confirmation
  • Ages 0.2 yrs - 89 yrs
  • Absence of above

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Connecticut Children's Medical Center

Hartford, Connecticut, 06103, United States

RECRUITING

Related Publications (23)

  • Germain-Lee EL, Groman J, Crane JL, Jan de Beur SM, Levine MA. Growth hormone deficiency in pseudohypoparathyroidism type 1a: another manifestation of multihormone resistance. J Clin Endocrinol Metab. 2003 Sep;88(9):4059-69. doi: 10.1210/jc.2003-030028.

    PMID: 12970262BACKGROUND

  • Germain-Lee EL, Ding CL, Deng Z, Crane JL, Saji M, Ringel MD, Levine MA. Paternal imprinting of Galpha(s) in the human thyroid as the basis of TSH resistance in pseudohypoparathyroidism type 1a. Biochem Biophys Res Commun. 2002 Aug 9;296(1):67-72. doi: 10.1016/s0006-291x(02)00833-1.

    PMID: 12147228BACKGROUND

  • Germain-Lee EL, Schwindinger W, Crane JL, Zewdu R, Zweifel LS, Wand G, Huso DL, Saji M, Ringel MD, Levine MA. A mouse model of albright hereditary osteodystrophy generated by targeted disruption of exon 1 of the Gnas gene. Endocrinology. 2005 Nov;146(11):4697-709. doi: 10.1210/en.2005-0681. Epub 2005 Aug 11.

    PMID: 16099856BACKGROUND

  • Levine MA, Germain-Lee E, Jan de Beur S. Genetic basis for resistance to parathyroid hormone. Horm Res. 2003;60 Suppl 3:87-95. doi: 10.1159/000074508.

    PMID: 14671404BACKGROUND

  • Jan de Beur S, Ding C, Germain-Lee E, Cho J, Maret A, Levine MA. Discordance between genetic and epigenetic defects in pseudohypoparathyroidism type 1b revealed by inconsistent loss of maternal imprinting at GNAS1. Am J Hum Genet. 2003 Aug;73(2):314-22. doi: 10.1086/377136. Epub 2003 Jul 11.

    PMID: 12858292BACKGROUND

  • Huso DL, Edie S, Levine MA, Schwindinger W, Wang Y, Juppner H, Germain-Lee EL. Heterotopic ossifications in a mouse model of albright hereditary osteodystrophy. PLoS One. 2011;6(6):e21755. doi: 10.1371/journal.pone.0021755. Epub 2011 Jun 29.

    PMID: 21747923BACKGROUND

  • Myllyla RM, Haapasaari KM, Palatsi R, Germain-Lee EL, Hagg PM, Ignatius J, Tuukkanen J. Multiple miliary osteoma cutis is a distinct disease entity: four case reports and review of the literature. Br J Dermatol. 2011 Mar;164(3):544-52. doi: 10.1111/j.1365-2133.2010.10121.x. Epub 2011 Feb 17.

    PMID: 21062265BACKGROUND

  • Mantovani G, Bastepe M, Monk D, de Sanctis L, Thiele S, Usardi A, Ahmed SF, Bufo R, Choplin T, De Filippo G, Devernois G, Eggermann T, Elli FM, Freson K, Garcia Ramirez A, Germain-Lee EL, Groussin L, Hamdy N, Hanna P, Hiort O, Juppner H, Kamenicky P, Knight N, Kottler ML, Le Norcy E, Lecumberri B, Levine MA, Makitie O, Martin R, Martos-Moreno GA, Minagawa M, Murray P, Pereda A, Pignolo R, Rejnmark L, Rodado R, Rothenbuhler A, Saraff V, Shoemaker AH, Shore EM, Silve C, Turan S, Woods P, Zillikens MC, Perez de Nanclares G, Linglart A. Diagnosis and management of pseudohypoparathyroidism and related disorders: first international Consensus Statement. Nat Rev Endocrinol. 2018 Aug;14(8):476-500. doi: 10.1038/s41574-018-0042-0.

    PMID: 29959430BACKGROUND

  • Mantovani G, Bastepe M, Monk D, de Sanctis L, Thiele S, Ahmed SF, Bufo R, Choplin T, De Filippo G, Devernois G, Eggermann T, Elli FM, Garcia Ramirez A, Germain-Lee EL, Groussin L, Hamdy NAT, Hanna P, Hiort O, Juppner H, Kamenicky P, Knight N, Le Norcy E, Lecumberri B, Levine MA, Makitie O, Martin R, Martos-Moreno GA, Minagawa M, Murray P, Pereda A, Pignolo R, Rejnmark L, Rodado R, Rothenbuhler A, Saraff V, Shoemaker AH, Shore EM, Silve C, Turan S, Woods P, Zillikens MC, Perez de Nanclares G, Linglart A. Recommendations for Diagnosis and Treatment of Pseudohypoparathyroidism and Related Disorders: An Updated Practical Tool for Physicians and Patients. Horm Res Paediatr. 2020;93(3):182-196. doi: 10.1159/000508985. Epub 2020 Aug 5.

    PMID: 32756064BACKGROUND

  • Crane JL, Shamblott MJ, Axelman J, Hsu S, Levine MA, Germain-Lee EL. Imprinting status of Galpha(s), NESP55, and XLalphas in cell cultures derived from human embryonic germ cells: GNAS imprinting in human embryonic germ cells. Clin Transl Sci. 2009 Oct;2(5):355-60. doi: 10.1111/j.1752-8062.2009.00148.x.

    PMID: 20443919BACKGROUND

  • Germain-Lee EL. Short stature, obesity, and growth hormone deficiency in pseudohypoparathyroidism type 1a. Pediatr Endocrinol Rev. 2006 Apr;3 Suppl 2:318-27.

    PMID: 16675931RESULT

  • Long DN, McGuire S, Levine MA, Weinstein LS, Germain-Lee EL. Body mass index differences in pseudohypoparathyroidism type 1a versus pseudopseudohypoparathyroidism may implicate paternal imprinting of Galpha(s) in the development of human obesity. J Clin Endocrinol Metab. 2007 Mar;92(3):1073-9. doi: 10.1210/jc.2006-1497. Epub 2006 Dec 12.

    PMID: 17164301RESULT

  • Hsu SC, Groman JD, Merlo CA, Naughton K, Zeitlin PL, Germain-Lee EL, Boyle MP, Cutting GR. Patients with mutations in Gsalpha have reduced activation of a downstream target in epithelial tissues due to haploinsufficiency. J Clin Endocrinol Metab. 2007 Oct;92(10):3941-8. doi: 10.1210/jc.2007-0271. Epub 2007 Jul 24.

    PMID: 17652219RESULT

  • Plagge A, Kelsey G, Germain-Lee EL. Physiological functions of the imprinted Gnas locus and its protein variants Galpha(s) and XLalpha(s) in human and mouse. J Endocrinol. 2008 Feb;196(2):193-214. doi: 10.1677/JOE-07-0544.

    PMID: 18252944RESULT

  • Long DN, Levine MA, Germain-Lee EL. Bone mineral density in pseudohypoparathyroidism type 1a. J Clin Endocrinol Metab. 2010 Sep;95(9):4465-75. doi: 10.1210/jc.2010-0498. Epub 2010 Jul 7.

    PMID: 20610593RESULT

  • Joseph AW, Shoemaker AH, Germain-Lee EL. Increased prevalence of carpal tunnel syndrome in albright hereditary osteodystrophy. J Clin Endocrinol Metab. 2011 Jul;96(7):2065-73. doi: 10.1210/jc.2011-0013. Epub 2011 Apr 27.

    PMID: 21525160RESULT

  • Muniyappa R, Warren MA, Zhao X, Aney SC, Courville AB, Chen KY, Brychta RJ, Germain-Lee EL, Weinstein LS, Skarulis MC. Reduced insulin sensitivity in adults with pseudohypoparathyroidism type 1a. J Clin Endocrinol Metab. 2013 Nov;98(11):E1796-801. doi: 10.1210/jc.2013-1594. Epub 2013 Sep 12.

    PMID: 24030943RESULT

  • Lin MH, Numbenjapon N, Germain-Lee EL, Pitukcheewanont P. Progressive osseous heteroplasia, as an isolated entity or overlapping with Albright hereditary osteodystrophy. J Pediatr Endocrinol Metab. 2015 Jul;28(7-8):911-8. doi: 10.1515/jpem-2014-0435.

    PMID: 25894639RESULT

  • Salemi P, Skalamera Olson JM, Dickson LE, Germain-Lee EL. Ossifications in Albright Hereditary Osteodystrophy: Role of Genotype, Inheritance, Sex, Age, Hormonal Status, and BMI. J Clin Endocrinol Metab. 2018 Jan 1;103(1):158-168. doi: 10.1210/jc.2017-00860.

    PMID: 29059381RESULT

  • Germain-Lee EL. Management of pseudohypoparathyroidism. Curr Opin Pediatr. 2019 Aug;31(4):537-549. doi: 10.1097/MOP.0000000000000783.

    PMID: 31145125RESULT

  • McMullan P, Maye P, Yang Q, Rowe DW, Germain-Lee EL. Parental Origin of Gsalpha Inactivation Differentially Affects Bone Remodeling in a Mouse Model of Albright Hereditary Osteodystrophy. JBMR Plus. 2021 Nov 16;6(1):e10570. doi: 10.1002/jbm4.10570. eCollection 2022 Jan.

    PMID: 35079678RESULT

  • McMullan P, Germain-Lee EL. Aberrant Bone Regulation in Albright Hereditary Osteodystrophy dueto Gnas Inactivation: Mechanisms and Translational Implications. Curr Osteoporos Rep. 2022 Feb;20(1):78-89. doi: 10.1007/s11914-022-00719-w. Epub 2022 Feb 28.

    PMID: 35226254RESULT

  • Krishnan N, McMullan P, Yang Q, Buscarello AN, Germain-Lee EL. Prevalence of Chiari malformation type 1 is increased in pseudohypoparathyroidism type 1A and associated with aberrant bone development. PLoS One. 2023 Jan 20;18(1):e0280463. doi: 10.1371/journal.pone.0280463. eCollection 2023.

    PMID: 36662765RESULT

Related Links

MeSH Terms

Conditions

PseudohypoparathyroidismPseudopseudohypoparathyroidismDwarfism, PituitaryBehavior

Condition Hierarchy (Ancestors)

Bone Diseases, MetabolicBone DiseasesMusculoskeletal DiseasesMetal Metabolism, Inborn ErrorsMetabolism, Inborn ErrorsGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesMetabolic DiseasesNutritional and Metabolic DiseasesCalcium Metabolism DisordersDwarfismBone Diseases, DevelopmentalBone Diseases, EndocrineHypopituitarismPituitary DiseasesHypothalamic DiseasesBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesEndocrine System Diseases

Study Officials

  • Emily L Germain-Lee, MD

    Connecticut Children's Medical Ctr. and Univ. of Connecticut School of Medicine

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Emily L Germain-Lee, MD

CONTACT

860-837-6719egermain@connecticutchildrens.org

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
OTHER
Intervention Model
SINGLE GROUP
Model Details: Natural history
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Prof of Pediatrics & Prof of Reconstructive Sciences, Director of Albright Center, Head of Academic Affairs & Research, Pediatric Endocrinology

Study Record Dates

First Submitted

September 13, 2005

First Posted

September 21, 2005

Study Start

January 1, 2003

Primary Completion (Estimated)

October 1, 2030

Study Completion (Estimated)

December 1, 2030

Last Updated

May 28, 2025

Record last verified: 2025-05

Locations

US(1)