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.

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 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.

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.

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.

Subjects were randomized to receive growth Human Growth Hormone (1-134) (Nutropin) for 16 weeks

All subjects were diagnosed with growth hormone deficiency using standard testing.

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.

Preliminary analysis did not work as intended and subsequent data were not collected from any participants (please see the detailed explanation in the Measure Description).

This arm received study drug for 16 weeks. There were no serious adverse events.

Subject presented to a local emergency room with atypical chest pain. His evaluation was negative including ECG and blood testing. He was discharged home, and continued the study.