Effects of Growth Hormone Administration on Cardiovascular Risk in Cured Acromegalics With Growth Hormone Deficiency

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Anne Klibanski, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00182091
First received: September 14, 2005
Last updated: April 26, 2012
Last verified: April 2012
  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:

  1. has effects on cardiovascular risk markers (special blood tests which indicate how healthy your heart and arteries are)
  2. affects the stiffness of the arteries
  3. affects your heart rate and the capacity of your heart to respond to changes in body position
  4. 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 (without any interventions).


Condition Intervention
Acromegaly
Growth Hormone Deficiency
Pituitary Disease
Drug: Recombinant human growth hormone
Drug: Saline

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
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:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Change in High-sensitivity C-reactive Protein [ Time Frame: baseline and 6 months ] [ Designated as safety issue: No ]
    Change in high-sensitivity C-reactive protein in the AcroGHD randomized to Growth Hormone and AcroGHD randomized to Placebo arms. Note that the AcroGHS and Active Acromegaly arms were not interventional arms and thus do not have outcome results.


Secondary Outcome Measures:
  • Change in Total Fat Mass [ Time Frame: baseline and 6 months ] [ Designated as safety issue: No ]
    Change in total fat mass in the AcroGHD randomized to Growth Hormone and AcroGHD randomized to Placebo arms. Note that the AcroGHS and Active Acromegaly arms were not interventional arms and thus do not have outcome results.

  • Change in Total Abdominal Adipose Tissue [ Time Frame: baseline and 6 months ] [ Designated as safety issue: No ]
    Change in total abdominal adipose tissue in the AcroGHD randomized to Growth Hormone and AcroGHD randomized to Placebo arms. Note that the AcroGHS and Active Acromegaly arms were not interventional arms and thus do not have outcome results.

  • Change in Visceral Abdominal Adipose Tissue [ Time Frame: baseline and 6 months ] [ Designated as safety issue: No ]
    Change in visceral abdominal adipose tissue in the AcroGHD randomized to Growth Hormone and AcroGHD randomized to Placebo arms. Note that the AcroGHS and Active Acromegaly arms were not interventional arms and thus do not have outcome results.


Enrollment: 75
Study Start Date: August 2004
Study Completion Date: December 2010
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: AcroGHD Randomized to Growth Hormone
Subjects with a history of acromegaly who are now growth hormone deficient, randomized to growth hormone. This is an interventional arm.
Drug: Recombinant human growth hormone
Starting dose based on age, sex, and estrogen status and ranged from 3-6 mcg/kg/day. GH doses were adjusted based on IGF-1 levels to target the mid-normal range for age.
Other Name: Genotropin; Pfizer, Inc.
Placebo Comparator: AcroGHD Randomized to Placebo
Subjects with a history of acromegaly who are now growth hormone deficient, randomized to placebo. This is an interventional arm.
Drug: Saline
To maintain study-subject blinding, doses were sham adjusted.
Other Name: Placebo
No Intervention: AcroGHS
No Intervention: Active Acromegaly

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 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 oral glucose tolerance test (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 GH-releasing hormone (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 (aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3x upper limit of normal (ULN) or creatinine level >2.5 mg/dl)
  • Congestive heart failure (New York Heart Association's classification system Class II-IV congestive heart failure (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
  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: NCT00182091

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Anne Klibanski, MD Massachusetts General Hospital
  More Information

Additional Information:
Publications:
Responsible Party: Anne Klibanski, MD, Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00182091     History of Changes
Other Study ID Numbers: 2004p-001078
Study First Received: September 14, 2005
Results First Received: February 7, 2012
Last Updated: April 26, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:
Acromegaly
Growth Hormone Deficiency
Cardiovascular Risk
Pituitary
Hypothalamic

Additional relevant MeSH terms:
Acromegaly
Dwarfism, Pituitary
Pituitary Diseases
Endocrine System Diseases
Bone Diseases, Endocrine
Bone Diseases
Musculoskeletal Diseases
Hyperpituitarism
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Dwarfism
Bone Diseases, Developmental
Hypopituitarism
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014