An Investigation of Pituitary Tumors and Related Hypothalmic Disorders

Cushing Disease Clinical Trial

Official title:

A Clinical and Genetic Investigation of Pituitary and HYPOTHALAMIC Tumors and Related Disorders

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00001595
• Other study ID #: 970076
• Secondary ID: 97-CH-0076
• Status: Recruiting
• Start date: April 21, 1997

Study information

• Verified date: December 15, 2023
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Samah M Agabein
• Phone: (301) 451-7615
• Email: samah.agabein[@]nih.gov
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

There is a variety of tumors affecting the pituitary gland in childhood; some of these tumors (eg craniopharyngioma) are included among the most common central nervous system tumors in childhood. The gene(s) involved in the pathogenesis of these tumors are largely not known; their possible association with other developmental defects or inheritance pattern(s) has not been investigated. The present study serves as a (i) screening/training, and, (ii) a research protocol.

As a screening and training study, this protocol allows our Institute to admit children with tumors of the hypothalamic-pituitary unit to the pediatric endocrine clinics and wards of the NIH Clinical Center for the purposes of

(i)<TAB>training our fellows and students in the identification of genetic defects associated with pituitary tumor formation, and

(ii)<TAB>teaching our fellows and students the recognition, management and complications of pituitary tumors

As a research study, this protocol aims at

(i)<TAB>developing new clinical studies for the recognition and therapy of pituitary tumors; as an example, two new studies have emerged within the context of this protocol: (a) investigation of a new research magnetic resonance imaging (MRI) tool and its usefulness in the identification of pituitary tumors, and (b) investigation of the psychological effects of cortisol secretion in pediatric patients with Cushing disease. Continuation of this protocol will eventually lead to new, separate protocols that will address all aspects of diagnosis of pituitary tumors and their therapy in childhood.

(ii)<TAB>Identifying the genetic components of pituitary oncogenesis; those will be investigated by (a) studying the inheritance pattern of pituitary tumors in childhood and their possible association with other conditions in the families of the patients, and (ii) collecting tumor tissues and examining their molecular genetics. As with the clinical studies, the present protocol may help generate ideas for future studies on the treatment and clinical follow up of pediatric patients with tumors of the pituitary gland and, thus, lead to the development of better therapeutic regimens for these neoplasms.

Description:

Study Description:

This protocol aims to evaluate subjects with tumors of the hypothalamic pituitary unit to:

identify genetic components of pituitary and hypothalamic oncogenesis, to develop new clinical studies for the recognition and therapy of pituitary tumors, and to investigate the psychological effects of cortisol secretion.

Objectives:

Primary Objective:

To collect peripheral blood DNA samples and tumor tissues and examine the molecular genetics of the specimens, in an effort to elucidate developmental pathways leading to pituitary gland oncogenesis and/or other defects.

Secondary Objectives:

To serve as a screening protocol for future studies on the treatment and clinical follow up of our patients with pituitary tumors; it is our hope that the protocol will continue to be a vehicle for the development of more related clinical studies.

To evaluate the cognitive, psychological, and patient-reported health status of mental and social well-being and symptoms of adrenal insufficiency associated with Cushing syndrome in children with this disease.

Endpoints:

Primary Endpoint:

Molecular genetic testing, whole exome sequencing

Secondary Endpoints:

Pre-post treatment comparison of research variables related to pituitary/hypothalamic tumors and comorbidities.

Cognitive, behavioral, psychological, and patient-reported outcomes

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2000
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 3 Years to 70 Years

Eligibility

• INCLUSION CRITERIA:

1. Stated willingness to comply with all study procedures and availability for the duration of the study

2. Male or female, aged 3 years to 70 years

3. Evidence for the existence of a tumor of the hypothalamic-pituitary unit, as indicated by previously obtained imaging studies or biochemical investigation of the hypothalamohypophyseal function.

4. Family members (any age) of patients with a family history of tumors and who will agree to participate in the DNA/linkage analysis study.

5. Member of a kindred suspected of having an inherited form of pituitary neoplasia, as evidenced by results of a patient enrolled in this protocol.

6. Ability of subject or Legally Authorized Representative (LAR)) to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

1. Pregnancy.

Related Conditions & MeSH terms

• Acromegaly
• ACTH-Secreting Pituitary Adenoma
• Cushing Disease
• Gigantism
• Gigantism/Acromegaly
• Panhypopituitarism
• Pituitary ACTH Hypersecretion
• Prolactinoma

Intervention

Procedure:
• MRI

• Tissue specimen collection

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Magiakou MA, Mastorakos G, Oldfield EH, Gomez MT, Doppman JL, Cutler GB Jr, Nieman LK, Chrousos GP. Cushing's syndrome in children and adolescents. Presentation, diagnosis, and therapy. N Engl J Med. 1994 Sep 8;331(10):629-36. doi: 10.1056/NEJM199409083311002. — View Citation

Stratakis CA, Carney JA, Lin JP, Papanicolaou DA, Karl M, Kastner DL, Pras E, Chrousos GP. Carney complex, a familial multiple neoplasia and lentiginosis syndrome. Analysis of 11 kindreds and linkage to the short arm of chromosome 2. J Clin Invest. 1996 Feb 1;97(3):699-705. doi: 10.1172/JCI118467. — View Citation

Trivellin G, Daly AF, Faucz FR, Yuan B, Rostomyan L, Larco DO, Schernthaner-Reiter MH, Szarek E, Leal LF, Caberg JH, Castermans E, Villa C, Dimopoulos A, Chittiboina P, Xekouki P, Shah N, Metzger D, Lysy PA, Ferrante E, Strebkova N, Mazerkina N, Zatelli MC, Lodish M, Horvath A, de Alexandre RB, Manning AD, Levy I, Keil MF, Sierra Mde L, Palmeira L, Coppieters W, Georges M, Naves LA, Jamar M, Bours V, Wu TJ, Choong CS, Bertherat J, Chanson P, Kamenicky P, Farrell WE, Barlier A, Quezado M, Bjelobaba I, Stojilkovic SS, Wess J, Costanzi S, Liu P, Lupski JR, Beckers A, Stratakis CA. Gigantism and acromegaly due to Xq26 microduplications and GPR101 mutation. N Engl J Med. 2014 Dec 18;371(25):2363-74. doi: 10.1056/NEJMoa1408028. Epub 2014 Dec 3. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Molecular genetic testing, whole exome sequencing	To collect peripheral blood DNA samples and tumor tissues and examine the molecular genetics of the specimens, in an effort to elucidate developmental pathways leading to pituitary gland oncogenesis and/or other defects.	ongoing
Secondary	To investigate the usefulness of a new MRI of the pituitary gland	Comparison of MRI techniques to identify micro adenomas	completed
Secondary	To identify the clinical and genetic features of pituitary tumors by investigating their inheritance pattern and possible association with other conditions in the families of the patients,	Genetic studies of pituitary and hypothalamic tumors or related disorders	ongoing
Secondary	To evaluate the cognitive, psychological, and patient-reported health status of mental and social well-being and symptoms of adrenal insufficiency associated with Cushing syndrome in children with this disease.	Descriptive study of cognitive, psychological, and patient-reported health status of mental and social well-being associated with Cushing and after treatment	ongoing
Secondary	to collect peripheral blood DNA samples and tumor tissues and examine the molecular genetics of the specimens, in an effort to elucidate developmental pathways leading to pituitary gland oncogenesis and/or other defects	Genetic studies of pituitary and hypothalamic tumors or related disorders	ongoing

External Links

•   NIH Clinical Center Detailed Web Page