SMART: Somatotrophics, Memory, and Aging Research Trial

NCT ID: NCT00257712

Last Updated: 2013-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

151 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-02-28

Study Completion Date

2011-12-31

Brief Summary

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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).

Detailed Description

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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.

Conditions

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Aging Mild Cognitive Impairment

Keywords

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Alzheimer's disease cognition disorders

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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1

Group Type EXPERIMENTAL

TH9507 human growth hormone releasing hormone (GHRH)

Intervention Type DRUG

1mg subcutaneous injection given daily for 20 weeks

2

Group Type PLACEBO_COMPARATOR

TH9507 human growth hormone releasing hormone (GHRH)

Intervention Type DRUG

1mg subcutaneous injection given daily for 20 weeks

Interventions

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TH9507 human growth hormone releasing hormone (GHRH)

1mg subcutaneous injection given daily for 20 weeks

Intervention Type DRUG

Eligibility Criteria

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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


* Memory complaint that can be corroborated by a study partner
* Memory test scores meeting the diagnostic criteria for MCI
* MMSE score greater than 20


* 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
Minimum Eligible Age

55 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Washington

OTHER

Sponsor Role lead

National Institute on Aging (NIA)

NIH

Sponsor Role collaborator

Responsible Party

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Michael Vitiello

PhD, Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Michael V. Vitiello, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Washington

Suzanne Barsness, RN,MSN,CCRC

Role: STUDY_DIRECTOR

University of Washington

Locations

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University of Washington

Seattle, Washington, United States

Site Status

Countries

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United States

References

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Merriam GR, Schwartz RS, Vitiello MV. Growth hormone-releasing hormone and growth hormone secretagogues in normal aging. Endocrine. 2003 Oct;22(1):41-8. doi: 10.1385/ENDO:22:1:41.

Reference Type BACKGROUND
PMID: 14610297 (View on PubMed)

Vitiello MV, Moe KE, Merriam GR, Mazzoni G, Buchner DH, Schwartz RS. Growth hormone releasing hormone improves the cognition of healthy older adults. Neurobiol Aging. 2006 Feb;27(2):318-23. doi: 10.1016/j.neurobiolaging.2005.01.010. Epub 2005 Mar 23.

Reference Type BACKGROUND
PMID: 16399214 (View on PubMed)

Friedman SD, Baker LD, Borson S, Jensen JE, Barsness SM, Craft S, Merriam GR, Otto RK, Novotny EJ, Vitiello MV. Growth hormone-releasing hormone effects on brain gamma-aminobutyric acid levels in mild cognitive impairment and healthy aging. JAMA Neurol. 2013 Jul;70(7):883-90. doi: 10.1001/jamaneurol.2013.1425.

Reference Type DERIVED
PMID: 23689947 (View on PubMed)

Baker LD, Barsness SM, Borson S, Merriam GR, Friedman SD, Craft S, Vitiello MV. Effects of growth hormone-releasing hormone on cognitive function in adults with mild cognitive impairment and healthy older adults: results of a controlled trial. Arch Neurol. 2012 Nov;69(11):1420-9. doi: 10.1001/archneurol.2012.1970.

Reference Type DERIVED
PMID: 22869065 (View on PubMed)

Other Identifiers

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R01AG025515

Identifier Type: NIH

Identifier Source: secondary_id

View Link

R01AG025525-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

28287-K

Identifier Type: -

Identifier Source: org_study_id