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

NCT00182091 | Completed Results DMC

• 1 other identifier: 2004p-001078
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Acromegaly; Growth Hormone Deficiency; Pituitary Disease

Keywords

Acromegaly; Growth Hormone Deficiency; Cardiovascular Risk; Pituitary; Hypothalamic

Outcome Measures

Primary Outcomes (1)

• Change in High-sensitivity C-reactive Protein

  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.

  baseline and 6 months

Secondary Outcomes (3)

• Change in Total Fat Mass

  baseline and 6 months

• Change in Total Abdominal Adipose Tissue

  baseline and 6 months

• Change in Visceral Abdominal Adipose Tissue

  baseline and 6 months

Study Arms (4)

AcroGHD Randomized to Growth Hormone

ACTIVE COMPARATOR

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

AcroGHD Randomized to Placebo

PLACEBO COMPARATOR

Subjects with a history of acromegaly who are now growth hormone deficient, randomized to placebo. This is an interventional arm.

Drug: Saline

AcroGHS

NO INTERVENTION

Active Acromegaly

NO INTERVENTION

Interventions

Recombinant human growth hormone DRUG

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.

Also known as: Genotropin; Pfizer, Inc.

AcroGHD Randomized to Growth Hormone

Saline DRUG

To maintain study-subject blinding, doses were sham adjusted.

Also known as: Placebo

AcroGHD Randomized to Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (3)

• Miller KK, Wexler T, Fazeli P, Gunnell L, Graham GJ, Beauregard C, Hemphill L, Nachtigall L, Loeffler J, Swearingen B, Biller BM, Klibanski A. Growth hormone deficiency after treatment of acromegaly: a randomized, placebo-controlled study of growth hormone replacement. J Clin Endocrinol Metab. 2010 Feb;95(2):567-77. doi: 10.1210/jc.2009-1611. Epub 2010 Jan 8.

  PMID: 20061426 RESULT

• Wexler T, Gunnell L, Omer Z, Kuhlthau K, Beauregard C, Graham G, Utz AL, Biller B, Nachtigall L, Loeffler J, Swearingen B, Klibanski A, Miller KK. Growth hormone deficiency is associated with decreased quality of life in patients with prior acromegaly. J Clin Endocrinol Metab. 2009 Jul;94(7):2471-7. doi: 10.1210/jc.2008-2671. Epub 2009 Apr 14.

  PMID: 19366847 RESULT

• Wexler TL, Durst R, McCarty D, Picard MH, Gunnell L, Omer Z, Fazeli P, Miller KK, Klibanski A. Growth hormone status predicts left ventricular mass in patients after cure of acromegaly. Growth Horm IGF Res. 2010 Oct;20(5):333-7. doi: 10.1016/j.ghir.2010.05.003. Epub 2010 Jul 3.

  PMID: 20598930 RESULT

MeSH Terms

Conditions

Acromegaly; Dwarfism, Pituitary; Pituitary Diseases

Interventions

Growth Hormone; Human Growth Hormone; Sodium Chloride

Condition Hierarchy (Ancestors)

Bone Diseases, Endocrine; Bone Diseases; Musculoskeletal Diseases; Hyperpituitarism; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Dwarfism; Bone Diseases, Developmental; Hypopituitarism

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Anterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Dr. Anne Klibanski
• Organization: Massachusetts General Hospital

617-726-3870

Study Officials

• Anne Klibanski, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief, Neuroendocrine Unit

Study Record Dates

• First Submitted: September 14, 2005
• First Posted: September 16, 2005
• Study Start: August 1, 2004
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2010
• Last Updated: September 2, 2020
• Results First Posted: May 28, 2012

Record last verified: 2020-08

Locations

US (1)