Effects of Growth Hormone on Cognition and Cerebral Metabolism in Adults With Growth Hormone Deficiency
Condition: Hypopituitarism
MeSH terms: Hypopituitarism
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): Human Growth Hormone (1-134); Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 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.; Subjects randomized to placebo
Other intervention name(s): Nutropin (brand name)
Intervention MeSH terms: Hormones
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment