- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00183092
CJD (Creutzfeldt-Jakob Disease) Quinacrine Study
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
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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California
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San Francisco, California, United States, 94143
- University of California, San Francisco
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Placebo Comparator: placebo
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100mg by mouth three times a day
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Experimental: quinacrine
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100mg by mouth three times a day
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Primary Survival
Time Frame: Randomization to Month-2
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Participants alive after 2 months on study treatment
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Randomization to Month-2
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Mini-Mental State Examination (MMSE) After 2 Months
Time Frame: Baseline to Month-2
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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.
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Baseline to Month-2
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Barthel Score Change After 2 Months
Time Frame: baseline, 2 months
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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.
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baseline, 2 months
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Change in Clinical Dementia Rating Scale Sum of Boxes (CDRS-SB) After 2 Months
Time Frame: Baseline, 2 months
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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.
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Baseline, 2 months
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Change in Rankin Score After 2 Months
Time Frame: Baseline, 2 months
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The scale runs from 0-6, running from perfect health without symptoms to death. 0 - No symptoms.
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Baseline, 2 months
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ADAS-Cog Change After 2 Months Among Survivors
Time Frame: Baseline, 2 months
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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.
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Baseline, 2 months
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Change in Phonemic Fluency (Words Beginning With Letter "D")
Time Frame: Baseline, 2 months
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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.
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Baseline, 2 months
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Change in Semantic Verbal Fluency (Naming Animals)
Time Frame: Baseline, 2 months
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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.
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Baseline, 2 months
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Collaborators and Investigators
Collaborators
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
Publications and helpful links
General Publications
- Prusiner SB. Prions. Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13363-83. doi: 10.1073/pnas.95.23.13363.
- Korth C, May BC, Cohen FE, Prusiner SB. Acridine and phenothiazine derivatives as pharmacotherapeutics for prion disease. Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9836-41. doi: 10.1073/pnas.161274798.
- Scoazec JY, Krolak-Salmon P, Casez O, Besson G, Thobois S, Kopp N, Perret-Liaudet A, Streichenberger N. Quinacrine-induced cytolytic hepatitis in sporadic Creutzfeldt-Jakob disease. Ann Neurol. 2003 Apr;53(4):546-7. doi: 10.1002/ana.10530. No abstract available.
- Wallace DJ. Is there a role for quinacrine (Atabrine) in the new millennium? Lupus. 2000;9(2):81-2. doi: 10.1191/096120300678828163. No abstract available.
- Engel GL. Quinacrine effects on the central nervous system. JAMA. 1966 Aug 8;197(6):515. No abstract available.
- Geschwind MD, Kuo AL, Wong KS, Haman A, Devereux G, Raudabaugh BJ, Johnson DY, Torres-Chae CC, Finley R, Garcia P, Thai JN, Cheng HQ, Neuhaus JM, Forner SA, Duncan JL, Possin KL, Dearmond SJ, Prusiner SB, Miller BL. Quinacrine treatment trial for sporadic Creutzfeldt-Jakob disease. Neurology. 2013 Dec 3;81(23):2015-23. doi: 10.1212/WNL.0b013e3182a9f3b4. Epub 2013 Oct 11.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Infections
- Neurocognitive Disorders
- Central Nervous System Infections
- Dementia
- Prion Diseases
- Creutzfeldt-Jakob Syndrome
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antineoplastic Agents
- Antiprotozoal Agents
- Antiparasitic Agents
- Antimalarials
- Antinematodal Agents
- Anthelmintics
- Antiplatyhelmintic Agents
- Anticestodal Agents
- Quinacrine
Other Study ID Numbers
- IA0083
- P01AG021601 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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