Effects of Growth Hormone on Cognition and Cerebral Metabolism in Adults With Growth Hormone Deficiency (GHD)
|ClinicalTrials.gov Identifier: NCT01007071|
Recruitment Status : Completed
First Posted : November 3, 2009
Results First Posted : November 17, 2017
Last Update Posted : November 17, 2017
|Condition or disease||Intervention/treatment||Phase|
|Hypopituitarism||Drug: Human Growth Hormone (1-134) Drug: Placebo||Phase 3|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||11 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||Effects of Growth Hormone on Cognition and Cerebral Metabolism in Adults|
|Actual Study Start Date :||November 1, 2009|
|Primary Completion Date :||December 12, 2012|
|Study Completion Date :||December 12, 2012|
Experimental: 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.
Drug: 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.
Other Name: Nutropin (brand name)
Placebo Comparator: 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.
Subjects randomized to placebo
- BOLD Signal Measured by Functional MRI Scan to Functional Connectivity Measured by fMRI [ Time Frame: Baseline and 16 weeks ]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.
- Neuropsychological Testing of Executive Function [ Time Frame: 16 weeks ]Executive function was assessed in part B of the 2-part Trail Making Test. In Part A, 25 circles are distributed over a sheet of paper, numbered 1 - 25, and the patient draws lines to connect the numbers in ascending order. In Part B, the circles include both numbers (1-13) and letters (A-L); as in Part A, the patient draws lines to connect the circles in an ascending pattern, but with the added task of alternating between the numbers and letters (i.e., 1-A-2-B-3-C, etc.). The patient is instructed to connect the circles as quickly as possible. The amount of time the patient takes to connect the circles is recorded as their score. If patients make an error, they are corrected then continue from the last correct circle. The number of seconds for completion of part B is reported, therefore higher scores reveal greater impairment.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01007071
|United States, California|
|Stanford University School of Medicine|
|Stanford, California, United States, 94305|
|Sub-Investigator:||Era Sidhaye Shah||Stanford University|
|Principal Investigator:||Laurence Katznelson||Stanford University|