SMART: Somatotrophics, Memory, and Aging Research Trial

University of Washington

Status and phase

Completed

Phase 2

Conditions

Aging

Mild Cognitive Impairment

Treatments

Drug: TH9507 human growth hormone releasing hormone (GHRH)

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00257712

28287-K

R01AG025525-01A1 (U.S. NIH Grant/Contract)

R01AG025515 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

The purpose of the SMART study was to better understand whether the body's own production of growth hormone (GH) would improve memory and problem solving ability, or cognitive function. The study was 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).

Full description

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 55-90, 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.

Enrollment

151 patients

Sex

All

Ages

55 to 90 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Able to give and understand informed consent
Able to communicate in English
No exclusionary criteria apply
Age between 55 and 90 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 greater than 20

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

Cognitive testing does not indicate MCI
MMSE score greater than 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 more than 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 greater than 150% ideal body weight
Tobacco use, excessive alcohol intake (more than 2 drinks per day), excessive caffeine intake (more than 4 cups of coffee per day)
Baseline IGF-I level greater than the mid-range for healthy young adults (250 ng/ml)
Meets NINCDS/ADRDA criteria for AD