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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Salena Killion, KineMed
ClinicalTrials.gov Identifier:
NCT01348061
First received: May 3, 2011
Last updated: May 16, 2013
Last verified: May 2013
  Purpose

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.


Condition
Alzheimer Disease
Progressive Supranuclear Palsy

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
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

Resource links provided by NLM:


Further study details as provided by KineMed:

Primary Outcome Measures:
  • Biomarker Measures [ Time Frame: Up to 32 days ] [ Designated as safety issue: No ]
    o Levels of deuterium-labeled chromogranin B, sAPPα and β-Trace in CSF


Secondary Outcome Measures:
  • Biomarker Measures [ Time Frame: Up to 32 days ] [ Designated as safety issue: No ]
    o Body water enrichment of deuterium in saliva and plasma (2H-enrichment(%))


Biospecimen Retention:   Samples With DNA

Whole blood


Enrollment: 16
Study Start Date: July 2011
Estimated Study Completion Date: July 2013
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts
Elderly Healthy Control (EHV)
No clinically significant deviation from healthy in medical history, physical examination, ECGs, MRI and clinical laboratory determinations for their respective age group.
Progressive Supranuclear Palsy (PSP)
A diagnosis of possible or probable PSP according to clinical criteria of National Institute of Neurologic Diseases and Stroke - the Society for PSP plus a MRI at screening to exclude other potential causes of parkinsonism as well as a mild-to-moderate stage of disease severity according to a score of 1 to 3 in Golbe Staging System.
Alzheimer's Disease (AD)
A diagnosis of probable AD Based on the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association and The Diagnostic and Statistical Manual of Mental Disorders as determined by a mini-mental state examination (MMSE) score of 16 to 26, inclusive.

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.

  Eligibility

Ages Eligible for Study:   50 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

AD, PSP and EHV subjects will be recruited via Contract Research Organizations (CROs). Recruitment efforts will target the general population residing in communities in proximity to the CROs.

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01348061

Locations
United States, California
Parexel
Glendale, California, United States, 91206
United States, New Jersey
Memory Enhancement Centers of America Inc.
Eatontown, New Jersey, United States, 07724
United States, Texas
Worldwide Clinical Trials
San Antonio, Texas, United States, 78217
Sponsors and Collaborators
Salena Killion
Bristol-Myers Squibb
Investigators
Study Director: Marc K Hellerstein, M.D., Ph.D. KineMed
  More Information

Additional Information:
No publications provided

Responsible Party: Salena Killion, Lab Manager, KineMed
ClinicalTrials.gov Identifier: NCT01348061     History of Changes
Other Study ID Numbers: CN167001
Study First Received: May 3, 2011
Last Updated: May 16, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by KineMed:
Alzheimers Disease
Progressive Supranuclear Palsy
CSF
Cerebrospinal Fluid
Biomarker
Heavy Water
Cargo proteins

Additional relevant MeSH terms:
Alzheimer Disease
Paralysis
Supranuclear Palsy, Progressive
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Neurologic Manifestations
Signs and Symptoms
Basal Ganglia Diseases
Movement Disorders
Ophthalmoplegia
Ocular Motility Disorders
Cranial Nerve Diseases
Eye Diseases

ClinicalTrials.gov processed this record on October 19, 2014