Clinical trial NCT00183092: CJD (Creutzfeldt-Jakob Disease) Quinacrine Study
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Creutzfeldt-Jakob Disease
Keywords: dementia
spongiform encephalopathy
nervous system disorder
acridine
prion
neuropharmacologic agent
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2005-09-16
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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 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)

Primary outcomes:
measure: Primary Survival
timeFrame: Randomization to Month-2
Secondary outcomes:
measure: Change in Mini-Mental State Examination (MMSE) After 2 Months
timeFrame: Baseline to Month-2
measure: Barthel Score Change After 2 Months
timeFrame: baseline, 2 months
measure: Change in Clinical Dementia Rating Scale Sum of Boxes (CDRS-SB) After 2 Months
timeFrame: Baseline, 2 months
measure: Change in Rankin Score After 2 Months
timeFrame: Baseline, 2 months
measure: ADAS-Cog Change After 2 Months Among Survivors
timeFrame: Baseline, 2 months
measure: Change in Phonemic Fluency (Words Beginning With Letter "D")
timeFrame: Baseline, 2 months
measure: Change in Semantic Verbal Fluency (Naming Animals)
timeFrame: Baseline, 2 months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
Study officials:
affiliation: UCSF Memory & Aging Center, University of California, San Francisco
name: Michael Geschwind, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: UCSF Memory & Aging Center, University of California, San Francisco
name: Bruce L. Miller, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Prusiner SB. Prions. Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13363-83. doi: 10.1073/pnas.95.23.13363.
citation: 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.
citation: 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.
citation: 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.
citation: Engel GL. Quinacrine effects on the central nervous system. JAMA. 1966 Aug 8;197(6):515. No abstract available.
citation: 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.