Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

CJD (Creutzfeldt-Jakob Disease) Quinacrine Study

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00183092
First received: September 14, 2005
Last updated: May 28, 2014
Last verified: May 2014
  Purpose

The purpose of this clinical trial is to determine the effectiveness of the medication quinacrine on survival in sporadic Creutzfeldt-Jakob disease (sCJD).


Condition Intervention Phase
Creutzfeldt-Jakob Disease
Drug: Quinacrine
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Novel Therapeutics For Prion Diseases: A Randomized, Double-blinded, Placebo-controlled Study of the Efficacy of Quinacrine in the Treatment of Sporadic Creutzfeldt-Jakob Disease

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Primary Survival [ Time Frame: Randomization to Month-2 ] [ Designated as safety issue: No ]
    Participants alive after 2 months on study treatment


Secondary Outcome Measures:
  • Change in Mini-Mental State Examination (MMSE) After 2 Months [ Time Frame: Baseline to Month-2 ] [ Designated as safety issue: No ]
    The mini-mental state examination (MMSE) is a brief 30-point questionnaire that is used to screen for cognitive impairment. In about 10 minutes it samples functions including arithmetic, memory and orientation. A score greater than or equal to 25 points (out of 30) indicates a normal cognition. Lower scores can indicate severe (≤9 points), moderate (10-18 points) or mild (19-24 points) cognitive impairment. Low to very low scores correlate closely with the presence of dementia, although other mental disorders can also lead to abnormal findings on MMSE testing.

  • Barthel Score Change After 2 Months [ Time Frame: baseline, 2 months ] [ Designated as safety issue: No ]
    An ordinal scale used to measure performance in activities of daily living. Scores range from 0 (worst, fully dependent) to 100 (best, independent); higher score associated with a greater likelihood of being able to live at home with a degree of independence following discharge from hospital. 10 individual items are scored and summed to derive the overall Barthel index score. Each item may be scored 0, 5, 10 or 15; not all items use the full range of 4 possible values. The amount of time and physical assistance required to perform each item are considered in scoring each item. For subjects unable to return for month-2 visit, Barthel Index was performed via telephone.

  • Change in Clinical Dementia Rating Scale Sum of Boxes (CDRS-SB) After 2 Months [ Time Frame: Baseline, 2 months ] [ Designated as safety issue: No ]
    Clinical Dementia Rating Scale Sum of Boxes (CDRS-SB). The CDR is obtained through semistructured interviews of patients and informants, and cognitive functioning is rated in 6 domains of functioning: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Each domain is rated on a 5-point scale of functioning: 0, no impairment; 0.5, questionable impairment; 1, mild impairment; 2, moderate impairment; and 3, severe impairment (personal care is scored on a 4-point scale without a 0.5 rating available). The global CDR score is computed via an algorithm. The CDR-SB score is obtained by summing each of the domain box scores, with scores ranging from 0 to 18. A higher value and/or positive change is worse. For subjects unable to return for month-2 visit, CDRS-SB was performed via telephone.

  • Change in Rankin Score After 2 Months [ Time Frame: Baseline, 2 months ] [ Designated as safety issue: No ]

    The scale runs from 0-6, running from perfect health without symptoms to death. 0 - No symptoms.

    1. - No significant disability. Able to carry out all usual activities, despite some symptoms.
    2. - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.
    3. - Moderate disability. Requires some help, but able to walk unassisted.
    4. - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.
    5. - Severe disability. Requires constant nursing care and attention, bedridden, incontinent.
    6. - Dead. For subjects unable to return for the 2-month visit, Rankin score was assessed via telephone.

  • ADAS-Cog Change After 2 Months Among Survivors [ Time Frame: Baseline, 2 months ] [ Designated as safety issue: No ]
    ADAS-cog measures cognitive performance by combining ratings of 11 components (word recall, word recognition, constructional praxis, orientation, naming objects and fingers, commands, ideational praxis, remembering instruction, spoken language, word finding, comprehension) representing six areas of cognition: memory; language; orientation to time, place and person; construction of simple designs and planning; and performing simple behaviors in pursuit of a basic, predefined goal. Seven components are scored as the 'number incorrect'. For example, in the commands component, the number of five commands performed incorrectly (range: 0-5). Four components are scored from 0 (no limitations) to 5 (max limitations) as the examiner's perception of remembering instructions, spoken language ability, word finding and comprehension. Component scores are summed into a total ADAS-cog score ranging from 0-75, with low scores indicating better cognitive performance.

  • Change in Phonemic Fluency (Words Beginning With Letter "D") [ Time Frame: Baseline, 2 months ] [ Designated as safety issue: No ]
    Verbal fluency tests are a kind of psychological test in which participants have to say as many words as possible from a category in 60 seconds. This category (words beginning with letter "D") is phonemic. Higher scores indicate better cognition.

  • Change in Semantic Verbal Fluency (Naming Animals) [ Time Frame: Baseline, 2 months ] [ Designated as safety issue: No ]
    Verbal fluency tests are a kind of psychological test in which participants have to say as many words as possible from a category in 60 seconds. This category (naming animals) is semantic. Higher scores indicate better cognition.


Enrollment: 69
Study Start Date: April 2005
Study Completion Date: June 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: quinacrine Drug: Quinacrine
100mg by mouth three times a day
Other Name: Atabrine
Placebo Comparator: placebo Drug: Placebo
100mg by mouth three times a day

Detailed Description:

Creutzfeldt-Jakob disease (CJD)is a rapidly progressive, invariably fatal and untreatable neurodegenerative disease with a mean duration of about eight months. Beyond the debilitating cognitive and motor deficits that accompany CJD, the difficulty in treating behavioral and mood disturbances and the rapidity of its course compound its tragedy. Recent results from experiments show that, at physiological concentrations, the anti-malarial drug quinacrine permanently clears abnormal prion proteins from cell culture. The demonstrated efficacy of quinacrine in cell culture, its relative safety and well known side-effects in the clinical setting, and the universal fatality of CJD justify quinacrine as an immediate candidate for the treatment of CJD.

The purpose of this clinical trial is to determine the efficacy of the medication quinacrine on survival in sporadic CJD (sCJD). This will be accomplished by bringing approximately 60 patients with probable or definite sCJD over approximately three years to UCSF for evaluation and initiation of a randomized, double-blinded, placebo-controlled (delayed treatment start) treatment study of quinacrine. Each patient will have a 50:50 chance of being placed on quinacrine or placebo upon study enrollment; however, all patients will be offered quinacrine after two months. Prior to study enrollment, patients will have a comprehensive clinical assessment to confirm the diagnosis of sCJD. Participants will come to UCSF for initial evaluation, potential study enrollment and, if possible, return to UCSF for follow-up at two and twelve months. Patients will receive telephone follow-up (every 2 weeks for the first two months and monthly thereafter) and local blood and testing to monitor for possible medication toxicity.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of probable or definite sCJD: Definite--biopsy confirmed sCJD; Probable--a progressive dementia with either a typical EEG or a typical MRI consistent with sCJD, and at least two of the following clinical features: myoclonus, pyramidal or extrapyramidal signs, visual symptoms, cerebellar signs, akinetic mutism, other focal higher cortical neurologic signs (e.g. neglect, apraxia, aphasia)
  • 18 years of age or older
  • Able to swallow
  • Able to follow simple one-step commands
  • Have had a brain MRI within 6 months and an EEG within 3 months ruling out other etiologies such as masses, strokes, or non-convulsive status epilepticus
  • Consent to autopsy in the event of their death during or after the study

Exclusion Criteria:

  • History of other significant or life-threatening disease, including: cancer; end-stage liver or renal disease; severe heart disease
  • History of other disease requiring regular supportive care
  • Liver disease
  • Active alcoholism
  • Bone marrow suppression
  • Severe hypotension
  • Severe psoriasis
  • Poorly controlled diabetes
  • Women who are pregnant or breast-feeding
  • Men, or women of childbearing age, not practicing reliable contraception
  • Serious allergies to quinacrine or other acridines
  • Current or recent use of quinacrine (within 6 months)
  • < 18 years of age
  • Any other contraindication to taking quinacrine
  • Genetic form of prion disease is identified prior to study enrollment
  • Current use of anti-arrhythmics (at discretion of investigator)
  • G6PD (Glucose 6-Phosphate Dehydrogenase) deficiency (at discretion of investigator)
  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: NCT00183092

Locations
United States, California
University of California, San Francisco
San Francisco, California, United States, 94143
Sponsors and Collaborators
University of California, San Francisco
Investigators
Principal Investigator: Michael Geschwind, MD, PhD UCSF Memory & Aging Center, University of California, San Francisco
Principal Investigator: Bruce L. Miller, MD UCSF Memory & Aging Center, University of California, San Francisco
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00183092     History of Changes
Other Study ID Numbers: IA0083, P01AG021601
Study First Received: September 14, 2005
Results First Received: January 21, 2014
Last Updated: May 28, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, San Francisco:
dementia
spongiform encephalopathy
nervous system disorder
acridine
prion
neuropharmacologic agent

Additional relevant MeSH terms:
Creutzfeldt-Jakob Syndrome
Brain Diseases
Central Nervous System Diseases
Central Nervous System Infections
Delirium, Dementia, Amnestic, Cognitive Disorders
Dementia
Mental Disorders
Nervous System Diseases
Prion Diseases
Quinacrine
Anthelmintics
Anti-Infective Agents
Anticestodal Agents
Antimalarials
Antinematodal Agents
Antineoplastic Agents
Antiparasitic Agents
Antiplatyhelmintic Agents
Antiprotozoal Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 23, 2014