The purpose of the SMART study is to better understand whether the body’s own production of growth hormone (GH) will improve memory and problem solving ability, or cognitive function. The study is a double blind, placebo-controlled study of the cognitive effects of growth hormone releasing hormone (GHRH) in healthy older men and women and in those with mild cognitive impairment (MCI).

Condition	Intervention	Phase
Aging Mild Cognitive Impairment	Drug: TH9507 human growth hormone releasing hormone (GHRH)	Phase II

Further study details as provided by National Institute on Aging (NIA):

Primary Outcomes: Change in declarative memory, including total recall scores on three tests of memory and on dual task response time (RT), a test of executive function.
Secondary Outcomes: Changes in other areas of cognitive function, including other tests of executive function, tests of lexical access, and tests of cognitive and perceptual-motor processing speed.
Expected Total Enrollment:  160

There is considerable and compelling evidence from both the animal and human literature that the actions of the somatotrophic hormonal axis (growth hormone releasing hormone/growth hormone/insulin-like growth factor I) have significant and predictable effects on cognitive function (memory and reasoning ability). A preliminary study has recently shown that five months of growth hormone releasing hormone (GHRH) treatment improves cognitive function in healthy older men and women; there is also preliminary evidence that supports the likelihood of a similar effect in individuals diagnosed with MCI.

The study sample will include 160 adults, ages 55-80, half of whom will be cognitively healthy normal adults and half of whom will meet diagnostic criteria for Mild Cognitive Impairment (MCI). Each of these groups will contain equal numbers of men and women. The treatment with GHRH will be twenty weeks in duration. In light of the documented interactions between estrogens and GHRH/GH/IGF-I, each of the two study arms will contain equal proportions of women not on estrogen replacement therapy (NERT) and women on oral estrogen replacement therapy (ERT). ERT women will maintain a regular steady dosage of estrogens for at least seven days preceding each assessment

Cognitive assessments to evaluate treatment-related changes in memory and thinking abilities, as well as blood collection to evaluate several biomarkers of interest, will be performed at baseline, 10 and 20 weeks of treatment, and ten weeks post-treatment. In addition there will be five medication and symptom monitoring visits during the treatment period.

The study hypotheses are:

H1: Healthy, cognitively normal older men and women treated with GHRH will show beneficial effects in cognitive function, including measures of memory, relative to placebo treated subjects.

H2: MCI patients treated with GHRH will show beneficial effects in cognitive function, including measures of memory, relative to placebo treated MCI patients.

H3: Changes in insulin-like-growth factor (IGF-I) will predict changes in cognition both for normal older adults and for MCI patients treated with GHRH.

Ages Eligible for Study:  55 Years   -   80 Years,  Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

Inclusion Criteria:

• Able to give and understand informed consent
• Able to communicate in English
• No exclusionary criteria apply
• Age between 55 and 80 years
• Independent in their daily living abilities
• Living at home with a reliable spouse, significant other or caregiver
• Normal PSA (for men) or mammogram (for women) within one year of study entry

The following inclusion criteria will be applied to identify potential MCI participants:

• Memory complaint that can be corroborated by a study partner
• Memory test scores meeting the diagnostic criteria for MCI
• MMSE score >24

The following inclusion criteria will be applied to identify potential normal control participants:

• Cognitive testing does not indicate MCI
• MMSE score > 28

Exclusion Criteria:

• Use of medications known to affect the GHRH/GH/IGF-I axis, including transdermal estrogens (use of oral estrogens is not contraindicated)
• Significant medical illness or organ failure, such as uncontrolled hypertension, diabetes, cardiac disease, cerebrovascular disease, chronic obstructive pulmonary disease, kidney and liver disease
• Significant neurologic disease that might affect cognition, such as Alzheimer’s disease, stroke, Parkinson’s disease, multiple sclerosis, severe head injury with loss of consciousness for >30 minutes or with permanent neurologic sequelae
• Personal or strong family history of cancer (especially colon, breast or melanoma)
• Evidence for pituitary disease by history or physical examination
• Symptoms or history of carpal tunnel or a positive Phalen’s Test
• Active arthritis
• Significant current psychiatric illness, such as depression, schizophrenia or an Axis II diagnosis suggestive of an inability to successfully complete the study protocol
• Current use of an anti-psychotic, anti-depressant, anti-convulsant, anti-coagulant, anxiolytic or sedative
• Current or planned use of DHEA, testosterone or cognition-enhancing medication (e.g., cholinesterase inhibitors, memantine)
• Weight >150% ideal body weight
• Tobacco use, excessive alcohol intake (>2 drinks/d), excessive caffeine intake (>4 cups of coffee/d)
• Baseline IGF-I level greater than the mid-range for healthy young adults (250 ng/ml)
• Meets NINCDS/ADRDA criteria for AD

Please refer to this study by ClinicalTrials.gov identifier  NCT00257712

Michael V. Vitiello, PhD      206-616-3444    vitiello@u.washington.edu

Washington
      University of Washington, Seattle,  Washington,  98195,  United States

Study chairs or principal investigators

Michael V. Vitiello, PhD,  Principal Investigator,  University of Washington   
Suzanne Barsness, RN,MSN,CCRC,  Study Director,  University of Washington   

Study ID Numbers:  IA0088; R01 AG025525-01 A1
Last Updated:  December 8, 2005
Record first received:  November 21, 2005
ClinicalTrials.gov Identifier:  NCT00257712
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2006-01-10