Cerebrospinal Fluid (CSF) Biomarkers Alzheimer's Disease (AD) and Non-AD Dementias

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01730430
Recruitment Status : Completed
First Posted : November 21, 2012
Last Update Posted : April 22, 2014
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Duke University

Brief Summary:
To establish a cutoff value using a ratio of CSF tau to Aβ42 (tau/Aβ42) for distinguishing patients wth mild to moderate Alzheimer's disease (AD) from health elderly control subjects. The investigators hypothesize that a cutoff can be found that has at least 80% sensitivity and 60% specificity.

Condition or disease
Alzheimer's Disease Dementias

Detailed Description:

This study will enroll 50 AD subjects, 50 normal controls and approximately 20 subjects with non-AD dementia. There will be 2 visits (up to 30 days apart), and a telephone follow-up visit.

This protocol does not include treatment of subjects. Lumbar puncture and phlebotomy are routine clinical tasks and are associated with a low level of risk. All adverse events will be documented and reviewed by the PI.

Study Type : Observational
Actual Enrollment : 40 participants
Observational Model: Case Control
Time Perspective: Cross-Sectional
Official Title: Investigation of Biomarkers of Disease State in Alzheimer's Disease and Non-AD Dementias
Study Start Date : July 2012
Actual Primary Completion Date : December 2013
Actual Study Completion Date : December 2013

Collection of CSF
  1. Those with Alzheimer's disease
  2. Those with non-Alzheimer's disease dementia
  3. Healthy elderly volunteers

Primary Outcome Measures :
  1. Ratio of CSF tau to Aβ42 (tau/Aβ42) [ Time Frame: CSF will be collected at Visit 1 (up to 30 days after the screening visit) ]
    CSF will be collected in clinic and shipped frozen to Merck's Clinical Development Lab for testing. Any remaining samples will be kept up to 20 years.

Biospecimen Retention:   Samples With DNA
Blood, urine and cerebral spinal fluid.

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Ages Eligible for Study:   55 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Duke Memory Disorders Clinic

Inclusion Criteria:

  • Each subject must be ≥ 55 to ≤ 85 years of age.
  • Each subject must be able to read at a 6th grade level, as determined by the investigator, and must have a history of academic achievement and/or employment sufficient to exclude mental retardation.
  • Each subject must have results of clinical laboratory tests, a physical examination, vital signs within normal limits or clinically acceptable to the investigator within 28 days prior to enrollment.
  • Each subject (or legal representative) must sign the informed consent form after the scope and nature of the investigation have been explained to them, and before screening assessments.

Additional Inclusion Criteria for Normal Controls:

  • Must have a global Clinical Dementia Rating (CDR) score of 0.
  • Must have a Mini-Mental State Examination (MMSE) score ≥ 28.
  • Must have a Z-score ≥ -1.0 in each cognitive domain of memory (including delayed recall), language, executive function and attention, and visuoconstruction with neuropsychological tests of choice and adjustment for age, gender, and education level if indicated.

Additional Inclusion Criteria for AD Subjects:

  • Must meet the criteria for a diagnosis of probable AD based on both

    1. the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria, and
    2. the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM IV TR) criteria for AD.
  • Must have an MMSE score ≥ 15 and ≤ 26.
  • Must have a clear history of cognitive and functional decline over at least one year that is either

    1. documented in medical records or
    2. documented by history from an informant who knows the subject well.
  • Must have an MRI or CT scan that is consistent with a diagnosis of AD within 12 months prior to enrollment.

Exclusion Criteria for AD Subjects and Normal Controls

  • The subject has a Rosen modified Hachinski Ischemia Score > 4.
  • The subject has a known history of stroke.
  • The subject has evidence of a clinically relevant or unstable neurological or psychiatric disorder (for AD subjects - other than AD).
  • The subject has a history of alcoholism or drug dependency/abuse within the last 5 years before enrollment.
  • The subject has an ongoing uncontrolled, clinically significant medical condition such that, in the judgment of the investigator, a subject's participation in the trial would pose a significant medical risk to the subject.
  • The subject has participated within the last two months in a clinical trial of a novel therapeutic agent (e.g. bapineuzumab) or has ever been in a clinical trial of an AD vaccine.
  • Pregnancy

Additional Inclusion and Exclusion Criteria for Subject with non-AD dementias

  • Standard clinical diagnostic criteria accepted by the field for non-AD dementias should be used by the Institution.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01730430

United States, North Carolina
Duke Health Center at Morreene Road
Durham, North Carolina, United States, 27705
Sponsors and Collaborators
Duke University
Merck Sharp & Dohme Corp.
Principal Investigator: James Burke, MD, PhD Duke UMC

Responsible Party: Duke University Identifier: NCT01730430     History of Changes
Other Study ID Numbers: Pro00033660
First Posted: November 21, 2012    Key Record Dates
Last Update Posted: April 22, 2014
Last Verified: April 2014

Keywords provided by Duke University:
non-AD dementias
healthy elderly controls

Additional relevant MeSH terms:
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders