Effects of Growth Hormone Administration on Cardiovascular Risk in Cured Acromegalics With Growth Hormone Deficiency - Full Text View

Sponsor:	Massachusetts General Hospital
Information provided by:	Massachusetts General Hospital
ClinicalTrials.gov Identifier:	NCT00182091

Sponsor:

Massachusetts General Hospital

Information provided by:

Massachusetts General Hospital

ClinicalTrials.gov Identifier:

NCT00182091

Purpose

The purpose of the study is to evaluate the effects of growth hormone (GH) replacement in men and women with a history of acromegaly and who are now growth hormone deficient. We will compare them to persons with a history of acromegaly who have normal GH levels.

Acromegaly results when an area in the brain, called the pituitary, produces too much growth hormone. When an individual is cured of acromegaly, the growth hormone levels may be normal or low (that is GH deficiency). Growth hormone deficiency means the body no longer produces as much growth hormone because the pituitary/hypothalamic region was damaged by a tumor or by treatment received.

We will study the effects of growth hormone replacement on the health of the heart and blood vessels of GH deficient persons by looking to see if this therapy:

has effects on cardiovascular risk markers (special blood tests which indicate how healthy your heart and arteries are)
affects the stiffness of the arteries
affects your heart rate and the capacity of your heart to respond to changes in body position
has different effects depending on whether you are taking estrogen / testosterone.

We will assess these measures of health on one occasion in persons with cured acromegaly and normal GH levels and in persons with cured acromegaly who have GH deficiency and a contraindication to receiving GH. GH deficient individuals with no contraindication to receiving GH, will participate in the study for 12 months. Individuals with normal GH levels, or who are GH deficient and have a contraindication to receiving GH, will be asked to return for one more visit.

Condition	Intervention
Acromegaly Growth Hormone Deficiency Pituitary Disease	Drug: Somatropin Drug: Placebo

Study Type:	Interventional
Study Design:	Treatment, Randomized, Single Blind (Subject), Placebo Control, Crossover Assignment, Efficacy Study
Official Title:	Effects of Physiologic Growth Hormone Administration on Cardiovascular Risk in Subjects With Growth Hormone Deficiency Following Cure of Acromegaly

Resource links provided by NLM:

Genetics Home Reference related topics: pseudoachondroplasia

MedlinePlus related topics: Pituitary Disorders

Drug Information available for: Somatropin Somatotropin

U.S. FDA Resources

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:

cardiovascular risk markers [ Time Frame: baseline, 3, 6, 9, and 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

heart rate variability and arterial distensibility [ Time Frame: baseline, 3, 6, 9, and 12 months ] [ Designated as safety issue: No ]
effects of GH depending upon gonadal status [ Time Frame: baseline, 1, 3, 6, 7, 9, and 12 months ] [ Designated as safety issue: No ]
body composition [ Time Frame: baseline, 3, 6, 9, and 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	160
Study Start Date:	August 2004
Estimated Study Completion Date:	December 2010
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator	Drug: Somatropin Stratified based on age, sex, and estrogen status: from 3 to 6 mcg/kg/day
2: Placebo Comparator	Drug: Placebo Stratified based on age, sex, and estrogen status: from 3 to 6 mcg/kg/day

Show Detailed Description

Eligibility

Ages Eligible for Study:	17 Years to 85 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age 18-75
History of acromegaly with biochemical cure documented with a normal OGTT and/or a non-elevated IGF-I without concurrent use of somatostatin analogs, dopamine agonists or GH receptor antagonists. Subjects will have been treated with medication, surgery, radiation, or a combination of these
At the time of enrollment a minimum of 6 months must have elapsed since surgery.
No malignancy on colonoscopy performed since the diagnosis of acromegaly
GHD due to surgical or radiation treatment
GHD will be defined as a peak plasma GH of less than 5 ng/ml in response to an insulin tolerance test or a GHRH plus arginine stimulation test
GHD will also be diagnosed if IGF-I levels are below 2 standard deviations for the age-sex normal range in a patient with at least two other documented anterior pituitary hormone deficiencies

Exclusion Criteria:

Untreated thyroid or adrenal insufficiency. Subjects on replacement therapy must be stable for at least 3 months prior to entry into the study
History of malignancy except for non-melanoma skin cancer
Hemoglobin <11.0 gm/dl
Uncontrolled hypertension
Hepatic or renal disease (AST/ALT > 3x ULN or creatinine level >2.5 mg/dl)
Congestive heart failure (New York Heart Association's classification system Class II-IV CHF will be excluded)
Unstable cardiovascular disease (coronary artery or cerebrovascular disease) or symptoms within one year prior to entry into the study
Initiation or discontinuation of gonadal steroid therapy within 3 months of entry
Diabetes mellitus, impaired fasting glucose, impaired glucose tolerance
Pregnancy or nursing
Active carpal tunnel syndrome
Subjects who have received GH therapy within one year prior to entry into the study
For female subjects age >40 a screening mammogram must have been obtained within one year prior to their baseline visit.
Sensitivity to m-cresol

United States, Massachusetts
Massachusetts General Hospital	Recruiting
Boston, Massachusetts, United States, 02114
Contact: Lindsay E Gunnell, BS 617-724-1579 lgunnell@partner.org
Contact: Tamara L. Wexler, MD 617-726-1347 twexler@partners.org
Principal Investigator: Anne Klibanski, MD

Responsible Party:	Massachusetts General Hospital / Harvard Medical School ( Anne Klibanski, MD )
Study ID Numbers:	2004p-001078
Study First Received:	September 14, 2005
Last Updated:	September 30, 2009
ClinicalTrials.gov Identifier:	NCT00182091 History of Changes
Health Authority:	United States: Food and Drug Administration