Effects of Growth Hormone on Cognition and Cerebral Metabolism in Adults With Growth Hormone Deficiency

NCT01007071 | Completed Phase 3 Results DMC

• 2 other identifiers: SU-10022009-4140IRB eprotocol # 15129
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with Growth hormone (GH) deficiency often report impaired quality of life and difficulty with mental functioning. It has been suggested that GH replacement in such patients leads to improvement in cognitive function. The aim of this study is to elucidate the effects of GH replacement in patients with GH deficiency on cognitive function using structural and functional neuroimaging and cognitive testing.

Conditions

Hypopituitarism

Outcome Measures

Primary Outcomes (1)

• BOLD Signal Measured by Functional MRI Scan to Functional Connectivity Measured by fMRI

  Functional MRI scans were to be performed at baseline and at 16 weeks. Changes in functional connectivity before and after 16 weeks of treatment were analyzed. The analysis involved approximately 40,000 paired sample t-tests. The dependent variable here for each subject is the correlation between the BOLD timeseries in the seed region (posterior cingulate cortex) and the BOLD timeseries in a given, standard space, brain voxel. This paired-sample t-test is run, separately, for every voxel in the brain. The pre-specified Outcome Measure intended to report the number of voxels that showed significant changes with active treatment. A preliminary analysis was conducted using a paired-sample t-test at each of the 40,000+ voxels, however, none of the voxels reached the level of significance. Since no significant voxels were detected, subsequent planned analyses were not performed, and summary level data cannot be reported for this Outcome Measure.

  Baseline and 16 weeks

Secondary Outcomes (1)

• Neuropsychological Testing of Executive Function

  16 weeks

Study Arms (2)

Growth hormone

EXPERIMENTAL

Subjects randomized to growth hormone (1-134) for 16 weeks. In this arm, growth hormone is dosed sc on a daily basis and increased over first 6 weeks (Men: start at 0.2 mg sc/d, increase to 0.6 mg sc/d after 4 weeks. Women, postmenopausal: start at 0.3 mg sc/d, increase to 0.9 mg sc/d after 4 weeks. Dose adjustments based on serum insulin-like growth factor-1 (IGF-1) levels at 6 and 12 weeks, with final IGF-1 measurement for efficacy performed at 16 weeks, with goal in range of -0.5 standard deviation (SD) to +2SD. An elevated serum IGF-1 value will result in a 20% dose reduction in GH in an active and random placebo patient. Similarly, a low serum IGF-1 will result in a 20% dose increase in an active and random placebo subject.

Drug: Human Growth Hormone (1-134)

Placebo

PLACEBO COMPARATOR

Subjects randomized to placebo for 16 weeks. As noted above, placebo subjects will be initiated on a daily subcutaneous injection, with dose changes based on changes in active drug subjects.

Drug: Placebo

Interventions

Human Growth Hormone (1-134) DRUG

Subjects randomized to human growth hormone (1-134) for 16 weeks. In this arm, growth hormone is dosed sc on a daily basis and increased over first 6 weeks (Men: start at 0.2 mg sc/d, increase to 0.6 mg sc/d after 4 weeks. Women, postmenopausal: start at 0.3 mg sc/d, increase to 0.9 mg sc/d after 4 weeks. Women premenopausal or on estrogen: start at 0.6 mg sc/d, increase to 1.3 mg sc/d after 4 weeks.) Dose adjustments based on serum IGF-1 levels at 6 and 12 weeks, with final IGF-1 measurement for efficacy performed at 16 weeks, with goal in range of -0.5 SD to +2SD. An elevated serum IGF-1 value will result in a 20% dose reduction in GH in an active and random placebo patient. Similarly, a low serum IGF-1 will result in a 20% dose increase in an active and random placebo subject.

Also known as: Nutropin (brand name)

Growth hormone

Placebo DRUG

Subjects randomized to placebo

Placebo

Eligibility Criteria

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

You may qualify if:

• Ability to provide written informed consent and comply with study assessments for the full duration of the study
• Age 18-65 years old
• Both men and women
• Naive to GH replacement therapy
• Diagnosis of Growth Hormone deficiency, adult onset
• Good general health
• Normal thyroid, adrenal or gonadal function, or stable thyroid, glucocorticoid (at replacement doses) and gonadal replacement therapy for at least 3 months prior to study initiation. If subjects are receiving transdermal testosterone, attainment of mid-normal serum values will be considered adequate. If subjects are on intramuscular testosterone, attainment of mid-normal serum testosterone at mid-injection cycle will be considered adequate

You may not qualify if:

• Pregnancy (positive pregnancy test) prior to enrollment in the study
• Any other condition that the investigator believes would pose a significant hazard to the subject if Growth Hormone therapy was initiated
• Idiopathic Growth Hormone Deficiency
• DSM IV diagnosis of Major Depressive Disorder with or without psychotic features, Bipolar II Disorder with or without psychotic features in a major depressive episode
• Current use of psychotropic medications
• History of moderate to severe brain injury
• Clinically significant cardiovascular disease
• Anemia with hct\<30
• Renal insufficiency with creatinine \>2.0
• Recent history of excessive alcohol use
• Participation in another simultaneous medical investigation or trial
• Active neoplasm
• Prader Willi Syndrome
• History of brain radiation
• Chemotherapy, past or present use

Sponsors & Collaborators

• Stanford University: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Hypopituitarism

Interventions

somatotropin (1-134); Human Growth Hormone

Condition Hierarchy (Ancestors)

Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Growth Hormone; Pituitary Hormones, Anterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Dr. Laurence Katznelson
• Organization: Stanford University

katznels@stanford.edu

650-736-9551

Study Officials

• Era Sidhaye Shah

  Stanford University

  SUB INVESTIGATOR

• Laurence Katznelson

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurosurgery and Medicine

Study Record Dates

• First Submitted: October 30, 2009
• First Posted: November 3, 2009
• Study Start: November 1, 2009
• Primary Completion: December 12, 2012
• Study Completion: December 12, 2012
• Last Updated: November 17, 2017
• Results First Posted: November 17, 2017

Record last verified: 2017-10

Locations

US (1)