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

NCT ID: NCT01007071

Last Updated: 2017-11-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-11-01
• Study Completion Date: 2012-12-12

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.

Detailed Description

Eligibility screening: Diagnosis of GHD will be based on standard testing, including a blunted GH response to stimulation with glucagon provocation, defined as GH <3 microgram/l. Subjects with adult-onset GH deficiency will be included if they are age 18-65 years old, naive to GH replacement therapy, in good general health, and on stable thyroid, glucocorticoid (at replacement doses) and gonadal replacement therapy for at least 6 weeks prior to study initiation. Patients with history a Major Depression will be excluded.

Baseline: Qualifying subjects will be admitted to the CTRU for the following: Weight, body mass index, waist/hip ratio, menstrual cycle history on female subjects and vital signs. Initial clinical laboratory assessments will include IGF-1, a complete blood count, liver function tests, free T4, and a serum pregnancy test for women. Subjects will undergo 3 hours of neuropsychological testing when attention, working memory, executive function and verbal memory will be assessed with the Wechsler Adult Intelligence Scale III and Wechsler Memory Scale (WMS III). Quality of life and mood will be quantified through the Quality of Life Scale, Hamilton Rating Scale for Depression and the Quality of Life Assessment of Growth Hormone Deficiency in Adults (Qol AGHDA). After a lunch break, the patients will undergo a 1 hour MRI scan. Resting images will be obtained, and thereafter simple letters, words or pictures will be projected to subjects while in the scanner. The subjects will be asked simple questions relating to these stimuli.

Randomization and treatment: Following completion of the baseline measurements, study participants will be randomized in a double blind fashion to receive either active treatment with GH or placebo for a period of 16 weeks. GH dosages will be increased incrementally over the first 6 weeks. At 16 weeks, all subjects randomized to placebo will be switched to GH in an open label fashion with dose schedules based on the above titration. Subjects initially randomized to GH will continue to receive GH with their endocrinologist without further follow up for the study.

For efficacy measures, neuropsychological testing and fMRI will be performed at baseline and at 16 weeks, and, for subjects initially randomized to placebo, repeat studies will be performed at 32 weeks.

Safety monitoring will include assessment of changes in thyroid and adrenal status, as well as changes in liver function.

Conditions

Hypopituitarism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Growth hormone

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.

Group Type: EXPERIMENTAL

Human Growth Hormone (1-134)

Intervention Type: 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.

Placebo

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Subjects randomized to placebo

Interventions

Human Growth Hormone (1-134)

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.

Intervention Type: DRUG

Placebo

Subjects randomized to placebo

Intervention Type: DRUG

Other Intervention Names

Nutropin (brand name)

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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
• History of head or eye injury involving persistent metal fragments, and implanted electrical device (such as a heart pacemaker)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Laurence Katznelson

Professor of Neurosurgery and Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Era Sidhaye Shah

Role: SUB_INVESTIGATOR

Stanford University

Laurence Katznelson

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University School of Medicine

Stanford, California, United States

Countries

United States

Other Identifiers

IRB eprotocol # 15129

Identifier Type: -

Identifier Source: secondary_id

SU-10022009-4140

Identifier Type: -

Identifier Source: org_study_id