The purpose of this clinical trial is to determine the effectiveness of the medication quinacrine on survival in sporadic Creutzfeldt-Jakob disease (sCJD).
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
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
69
100mg by mouth three times a day
100mg by mouth three times a day
University of California, San Francisco
San Francisco, California, United States
Primary Survival
Participants alive after 2 months on study treatment
Time frame: Randomization to Month-2
Change in Mini-Mental State Examination (MMSE) After 2 Months
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.
Time frame: Baseline to Month-2
Barthel Score Change After 2 Months
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.
Time frame: baseline, 2 months
Change in Clinical Dementia Rating Scale Sum of Boxes (CDRS-SB) After 2 Months
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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Time frame: Baseline, 2 months
Change in Rankin Score After 2 Months
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.
Time frame: Baseline, 2 months
ADAS-Cog Change After 2 Months Among Survivors
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.
Time frame: Baseline, 2 months
Change in Phonemic Fluency (Words Beginning With Letter "D")
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.
Time frame: Baseline, 2 months
Change in Semantic Verbal Fluency (Naming Animals)
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.
Time frame: Baseline, 2 months