Evaluating Cerebrospinal Fluid Biomarkers in Alzheimer’s, Progressive Supranuclear Palsy Subjects, and Controls

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Brief Title

Evaluating Cerebrospinal Fluid Biomarkers in Alzheimer's, Progressive Supranuclear Palsy Subjects, and Controls

Official Title

Experimental Medicine Study to Evaluate the Kinetics of Cerebrospinal Fluid Biomarkers in Subjects With Alzheimer's Disease and Progressive Supranuclear Palsy Compared to Healthy Subjects Using a Heavy Water Labeling Method

Brief Summary

      This is an experimental medicine study to evaluate the kinetics of cerebrospinal fluid (CSF)
      biomarkers in subjects with Alzheimer's disease (AD) or progressive supranuclear palsy (PSP)
      compared to healthy controls using a heavy water (2H2O) labeling method. This study is
      exploring the time profile of appearance and disappearance of pulse deuterium-labeled cargo
      proteins in CSF of subjects with AD and/or PSP, which is different from healthy controls, due
      to deficits in fast axonal transport.
    

Detailed Description

      Primary Objective:

      To compare the time profile of appearance and disappearance in CSF of pulse deuterium-labeled
      chromogranin B, sAPPα and β-Trace in AD and PSP subjects compared to healthy controls.

      Secondary Objectives:

        -  To measure body water enrichment of deuterium in saliva and plasma (2H-enrichment (%))

        -  To explore the effect of age on the kinetics of deuterium labeling of CSF biomarkers

        -  To assess intra and inter subject variability of deuterium-labeling of chromogranin B,
           sAPPα and β-Trace

      Subjects will undergo screening evaluations to determine eligibility prior to heavy water
      (2H20) administration. Eligible subjects will be admitted to the clinical facility on Day -1.
      On Day 1, subjects will ingest small doses of 2H20 during their inpatient stay. They will
      also drink 2H20 for 7 more days. Subjects will undergo two lumbar punctures (LPs) for CSF
      samples. Subjects will return to the study site approximately 7 days after the last LP (or
      early termination) for a follow-up assessment and discharge.
    


Study Type

Observational


Primary Outcome

Biomarker Measures

Secondary Outcome

 Biomarker Measures

Condition

Alzheimer Disease


Study Arms / Comparison Groups

 Elderly Healthy Control (EHV)
Description:  No clinically significant deviation from healthy in medical history, physical examination, ECGs, MRI and clinical laboratory determinations for their respective age group.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information



Estimated Enrollment

16

Start Date

July 2011

Completion Date

July 2013

Primary Completion Date

July 2013

Eligibility Criteria

        Inclusion Criteria:

        All subjects

          -  Body Mass Index of 18-32.

          -  Subjects can have common non-neurological age-related disorders (hypertension,
             diabetes) and on stable medication for the last 3 months.

          -  Screening score of < 4 on the Modified Hachinski Ischemia Scale.

          -  Women not of childbearing potential and men.

          -  Women with negative pregnancy test prior to starting heavy water and not
             breastfeeding.

        AD

          -  Diagnosis of probable AD.

          -  Mild to moderate disease severity according to mini-mental state examination score
             (MMSE) of 16-26.

          -  Documented cognitive decline began 6 months prior to screening.

          -  On stable doses of approved AD medications for 2 months prior to screening.

          -  Non-medicated AD subjects are free of AD medications for 2 months prior to screening.

          -  Mild to moderate white matter disease and up to 2 lacunar infarcts acceptable as
             determined by brain MRI at screening.

          -  Investigator determines subjects to be medically stable and physically able to
             complete the study.

          -  Minimum of 6 years of education and able to read, write and communicate effectively.

          -  Adequate hearing, vision, and language skills.

          -  Subjects and their caregivers must agree to the dosage regimens and procedures, report
             for scheduled visits, and communicate with study personnel.

        PSP

          -  Diagnosis of probable PSP.

          -  Brain MRI at screening excluding potential causes of parkinsonism, especially
             cerebrovascular and space occupying lesions.

          -  Mild-to-moderate stage of disease severity by a Golbe Staging System score of 1-3.

          -  Subjects and their caregivers must agree to the dosage regimens and procedures, report
             for scheduled visits, and communicate with study personnel.

          -  Currently on stable doses of PSP medications for 2 months prior to screening.

          -  Investigator determines subjects to be medically stable and able to complete the
             study.

          -  Minimum of 6 years of education and able to read, write and communicate effectively.

          -  Adequate hearing, vision, and language skills.

        EHV

          -  No clinically significant deviation from healthy for their age group.

          -  No subjective or objective memory loss.

          -  MMSE score of 28 to 30.

        Exclusion Criteria:

          -  Diseased subjects with a medical condition (not AD or PSP) that could contribute to
             the subjects dementia or Parkinsonism.

          -  History of pallidotomy, thalamotomy, active DBS or fetal tissue transplant.

          -  Any significant acute or chronic illness.

          -  Major surgery within 4 weeks of Day 1.

          -  Blood/plasma donation to a blood bank or a clinical study (except a screening visit)
             within 4 weeks of Day 1.

          -  Blood transfusion within 4 weeks of Day 1.

          -  Inability to be venipunctured.

          -  Inability to be lumbar punctured or contraindications to lumbar puncture or epidurals.

          -  > 10 cigarettes/day.

          -  Recent drug or alcohol abuse or positive urine screen for drugs of abuse.

          -  Subjects deemed inappropriate to undergo a MRI.

          -  Any medical, psychiatric or social reason as determined by the investigator.

          -  AD subjects with a history of CSF or amyloid imaging studies not consistent with
             Alzheimer's pathology.

          -  Healthy subjects with a history of CSF or amyloid imaging studies consistent with
             Alzheimer's pathology.

          -  Allergies to local anesthetics.

          -  Any significant drug allergy.
      

Gender

All

Ages

50 Years - 85 Years

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Marc K Hellerstein, M.D., Ph.D., , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT01348061

Organization ID

CN167001


Responsible Party

Principal Investigator

Study Sponsor

KineMed

Collaborators

 Bristol-Myers Squibb

Study Sponsor

Marc K Hellerstein, M.D., Ph.D., Study Director, KineMed


Verification Date

October 2014