Creutzfeldt-Jakob DiseasePhase 2NCT00183092
CJD (Creutzfeldt-Jakob Disease) Quinacrine Study
A Phase 2 study testing Quinacrine in people with Creutzfeldt-Jakob Disease, run by University of California, San Francisco at 1 site in United States.
Trial summary
The purpose of this clinical trial is to determine the effectiveness of the medication quinacrine on survival in sporadic Creutzfeldt-Jakob disease (sCJD). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Creutzfeldt-Jakob Disease
- What is being tested?
- Quinacrine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 69 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2005to Jun 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 17Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Francisco
San Francisco, California, 94143
About this 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
The purpose of this clinical trial is to determine the effectiveness of the medication quinacrine on survival in sporadic Creutzfeldt-Jakob disease (sCJD).
Read the 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.
- Conditions
- Creutzfeldt-Jakob Disease
- Being tested
- Quinacrine, Placebo
- Keywords
- dementia, spongiform encephalopathy, nervous system disorder, acridine, prion, neuropharmacologic agent
- Medical subject headings
- Creutzfeldt-Jakob Syndrome, Dementia, Prion Diseases, Nervous System Diseases, Insomnia, Fatal Familial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
QuinacrineDrug
Also called Atabrine
100mg by mouth three times a day
PlaceboDrug
100mg by mouth three times a day
| Study group | Role | What they receive |
|---|---|---|
| quinacrine | Experimental | Not described Receives: Drug: Quinacrine |
| placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Survival
Participants alive after 2 months on study treatment
Measured: Randomization to Month-2
Secondary outcomes (7)
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.
Measured: 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.
Measured: 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.
Measured: 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.
- - No significant disability. Able to carry out all usual activities, despite some symptoms.
- - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.
- - Moderate disability. Requires some help, but able to walk unassisted.
- - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.
- - Severe disability. Requires constant nursing care and attention, bedridden, incontinent.
- - Dead. For subjects unable to return for the 2-month visit, Rankin score was assessed via telephone.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline, 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2005 (estimated)
- Study startApr 2005
- Primary completionJun 2012
- Study completionJun 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Creutzfeldt-Jakob DiseaseStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 69 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Michael Geschwind, MD, PhD, Principal investigator, UCSF Memory & Aging Center, University of California, San FranciscoBruce L. Miller, MD, Principal investigator, UCSF Memory & Aging Center, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00183092
- Sponsor's protocol ID
- IA0083
- Other IDs
- P01AG021601
- Status last verified
- May 2014
- First submitted
- 14 Sep 2005
- Last updated
- 9 Jun 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 9811807Korth 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.
PubMed 11504948Scoazec 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.
PubMed 12666126Wallace 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.
PubMed 10787002Engel GL. Quinacrine effects on the central nervous system. JAMA. 1966 Aug 8;197(6):515. No abstract available.
PubMed 5952734Geschwind 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.
PubMed 24122181
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00183092
- Acronym / sponsor ID
- IA0083
- Conditions
- Creutzfeldt-Jakob Disease
- Keywords
- dementia, spongiform encephalopathy, nervous system disorder, acridine, prion, neuropharmacologic agent
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 69 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- Apr 2005
- Primary completion
- Jun 2012 (actual)
- Study completion
- Jun 2012 (actual)
- First posted
- 16 Sep 2005 (estimated)
- Results
- Posted 29 May 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| quinacrine | Experimental | Drug: Quinacrine |
| placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| QuinacrineAlso: Atabrine100mg by mouth three times a day | Drug | quinacrine |
| Placebo100mg by mouth three times a day | Drug | placebo |
Primary outcome
Primary Survival
Time frame: Randomization to Month-2
Participants alive after 2 months on study treatment
7 secondary outcomes
Change in Mini-Mental State Examination (MMSE) After 2 Months
Time frame: Baseline to Month-2
Barthel Score Change After 2 Months
Time frame: baseline, 2 months
Change in Clinical Dementia Rating Scale Sum of Boxes (CDRS-SB) After 2 Months
Time frame: Baseline, 2 months
Change in Rankin Score After 2 Months
Time frame: Baseline, 2 months
ADAS-Cog Change After 2 Months Among Survivors
Time frame: Baseline, 2 months
Change in Phonemic Fluency (Words Beginning With Letter "D")
Time frame: Baseline, 2 months
Change in Semantic Verbal Fluency (Naming Animals)
Time frame: Baseline, 2 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 9811807Prusiner SB. Prions. Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13363-83. doi: 10.1073/pnas.95.23.13363.
- Background: PubMed 11504948Korth 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.
- Background: PubMed 12666126Scoazec 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.
- Background: PubMed 10787002Wallace 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.
- Background: PubMed 5952734Engel GL. Quinacrine effects on the central nervous system. JAMA. 1966 Aug 8;197(6):515. No abstract available.
- Derived from this study: PubMed 24122181Geschwind 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.
- UCSF Memory \& Aging CenterLink provided by the sponsor.
- UCSF Institute for Neurodegenerative DiseasesLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Geschwind, MD, PhD principal investigator
UCSF Memory & Aging Center, University of California, San Francisco
Bruce L. Miller, MD principal investigator
UCSF Memory & Aging Center, University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Quinacrine in people with Creutzfeldt-Jakob Disease, run by University of California, San Francisco at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 May 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary Survival (time frame: Randomization to Month-2). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00183092, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jun 2014.