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

NCT01348061 | Completed

• 1 other identifier: CN167001
• Study Type: observational
• Target: 16
• Locations: 1 country
• Sites: 3

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.

Conditions

Alzheimer Disease; Progressive Supranuclear Palsy

Keywords

Alzheimers Disease; Progressive Supranuclear Palsy; CSF; Cerebrospinal Fluid; Biomarker; Heavy Water; Cargo proteins

Outcome Measures

Primary Outcomes (1)

• Biomarker Measures

  o Levels of deuterium-labeled chromogranin B, sAPPα and β-Trace in CSF

  Up to 32 days

Secondary Outcomes (1)

• Biomarker Measures

  Up to 32 days

Study Arms (3)

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.

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• KineMed: lead
• Bristol-Myers Squibb: collaborator

Study Sites (3)

Parexel

Glendale, California, 91206, United States

Location

Memory Enhancement Centers of America Inc.

Eatontown, New Jersey, 07724, United States

Location

Worldwide Clinical Trials

San Antonio, Texas, 78217, United States

Location

Related Links

• Related Info

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood

MeSH Terms

Conditions

Alzheimer Disease; Supranuclear Palsy, Progressive

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Basal Ganglia Diseases; Movement Disorders; Ophthalmoplegia; Ocular Motility Disorders; Cranial Nerve Diseases; Paralysis; Neurologic Manifestations; Eye Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Marc K Hellerstein, M.D., Ph.D.

  KineMed

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Clinical Studies

Study Record Dates

• First Submitted: May 3, 2011
• First Posted: May 5, 2011
• Study Start: July 1, 2011
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: October 24, 2014

Record last verified: 2014-10

Locations

US (3)