Trial Outcomes & Findings for CJD (Creutzfeldt-Jakob Disease) Quinacrine Study (NCT NCT00183092)
NCT ID: NCT00183092
Last Updated: 2014-06-09
Results Overview
Participants alive after 2 months on study treatment
COMPLETED
PHASE2
69 participants
Randomization to Month-2
2014-06-09
Participant Flow
Enrollment began in April 2005 and ended in January 2009. Subjects came from across the USA, as well as Canada, with a plurality from California, and enrolled at one U.S. clinical site (University of California, San Francisco).
425 patients referred; 69 subjects consented/enrolled; 54 subjects eligible/randomized; 3 randomized subjects identified as carriers of PrP (prion protein) gene mutations as determined by analysis of sequence variability of the bovine prion protein gene (PRNP) and excluded from analyses.
Participant milestones
| Measure |
Quinacrine
Double Blind Period: 100mg Quinacrine by mouth three times a day. Open Label Period: Choice of study drug or open-label Quinacrine 100mg by mouth three times a day.
|
Placebo
Double Blind Period: 100mg Placebo by mouth three times a day. Open Label Period: Choice of study drug or Quinacrine 100mg by mouth three times a day.
|
Study Drug (Quinacrine) During Open-Label Period
Participants received Quinacrine during Double-Blind period and opted to continue study drug during Open-Label period
|
Study Drug (Placebo) During Open-Label Period
Participants received Placebo during Double-Blind period and opted to continue study drug during Open-Label period
|
|---|---|---|---|---|
|
Double-blind (Baseline - Month 2)
STARTED
|
23
|
28
|
0
|
0
|
|
Double-blind (Baseline - Month 2)
Alive at Month 2
|
13
|
19
|
0
|
0
|
|
Double-blind (Baseline - Month 2)
Came in for Month 2 Visit
|
10
|
16
|
0
|
0
|
|
Double-blind (Baseline - Month 2)
COMPLETED
|
11
|
16
|
0
|
0
|
|
Double-blind (Baseline - Month 2)
NOT COMPLETED
|
12
|
12
|
0
|
0
|
|
Open-label Period (Month 2 Until Death)
STARTED
|
10
|
14
|
1
|
1
|
|
Open-label Period (Month 2 Until Death)
COMPLETED
|
0
|
0
|
0
|
0
|
|
Open-label Period (Month 2 Until Death)
NOT COMPLETED
|
10
|
14
|
1
|
1
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
CJD (Creutzfeldt-Jakob Disease) Quinacrine Study
Baseline characteristics by cohort
| Measure |
Placebo
n=28 Participants
Placebo : 100mg by mouth three times a day
|
Quinacrine
n=23 Participants
Quinacrine : 100mg by mouth three times a day
|
Total
n=51 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
64.4 years
FULL_RANGE 10.9 • n=5 Participants
|
60.5 years
FULL_RANGE 8.0 • n=7 Participants
|
62.5 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
28 participants
n=5 Participants
|
23 participants
n=7 Participants
|
51 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Randomization to Month-2Participants alive after 2 months on study treatment
Outcome measures
| Measure |
Placebo
n=28 Participants
Placebo : 100mg by mouth three times a day
|
Quinacrine
n=23 Participants
Quinacrine : 100mg by mouth three times a day
|
|---|---|---|
|
Primary Survival
|
19 participants
|
13 participants
|
SECONDARY outcome
Timeframe: Baseline to Month-2Population: Subjects still alive, who attended the month-2 visit and were willing and able to tolerate cognitive testing. 1 subject in each arm did attend the 2-month visit but did not cooperate fully with the MMSE, which was therefore not scored.
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.
Outcome measures
| Measure |
Placebo
n=15 Participants
Placebo : 100mg by mouth three times a day
|
Quinacrine
n=9 Participants
Quinacrine : 100mg by mouth three times a day
|
|---|---|---|
|
Change in Mini-Mental State Examination (MMSE) After 2 Months
|
-6.9 units on a scale
Interval -18.0 to 4.0
|
-3.9 units on a scale
Interval -10.0 to 1.0
|
SECONDARY outcome
Timeframe: baseline, 2 monthsPopulation: One surviving subject in the quinacrine arm did not attend the 2-month visit and was lost-to-followup; for a second surviving subject in the quinacrine arm, the Barthel Index was inadvertently not performed at the 2-month visit.
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.
Outcome measures
| Measure |
Placebo
n=19 Participants
Placebo : 100mg by mouth three times a day
|
Quinacrine
n=11 Participants
Quinacrine : 100mg by mouth three times a day
|
|---|---|---|
|
Barthel Score Change After 2 Months
|
-23.2 units on a scale
Interval -85.0 to 70.0
|
-13.2 units on a scale
Interval -65.0 to 5.0
|
SECONDARY outcome
Timeframe: Baseline, 2 monthsPopulation: For subjects still alive at month 2 and assessed at the 2-month visit or via telephone
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.
Outcome measures
| Measure |
Placebo
n=19 Participants
Placebo : 100mg by mouth three times a day
|
Quinacrine
n=12 Participants
Quinacrine : 100mg by mouth three times a day
|
|---|---|---|
|
Change in Clinical Dementia Rating Scale Sum of Boxes (CDRS-SB) After 2 Months
|
3.2 units on a scale
Interval -1.0 to 8.0
|
0.3 units on a scale
Interval -1.0 to 2.0
|
SECONDARY outcome
Timeframe: Baseline, 2 monthsPopulation: For subjects still alive at month 2 and assessed at the 2-month visit or via telephone
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.
Outcome measures
| Measure |
Placebo
n=19 Participants
Placebo : 100mg by mouth three times a day
|
Quinacrine
n=12 Participants
Quinacrine : 100mg by mouth three times a day
|
|---|---|---|
|
Change in Rankin Score After 2 Months
|
0.8 units on a scale
Interval 0.0 to 2.0
|
0.3 units on a scale
Interval -1.0 to 2.0
|
SECONDARY outcome
Timeframe: Baseline, 2 monthsPopulation: Subjects still alive and able to tolerate cognitive testing at Month 2 visit.
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.
Outcome measures
| Measure |
Placebo
n=9 Participants
Placebo : 100mg by mouth three times a day
|
Quinacrine
n=4 Participants
Quinacrine : 100mg by mouth three times a day
|
|---|---|---|
|
ADAS-Cog Change After 2 Months Among Survivors
|
13.0 units on a scale
Interval 0.0 to 23.0
|
12.6 units on a scale
Interval -2.0 to 37.0
|
SECONDARY outcome
Timeframe: Baseline, 2 monthsPopulation: Subject still alive and able to tolerate cognitive testing at month 2 visit
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.
Outcome measures
| Measure |
Placebo
n=9 Participants
Placebo : 100mg by mouth three times a day
|
Quinacrine
n=5 Participants
Quinacrine : 100mg by mouth three times a day
|
|---|---|---|
|
Change in Phonemic Fluency (Words Beginning With Letter "D")
|
-2.4 number of words generated
Interval -8.0 to 1.0
|
-2.2 number of words generated
Interval -5.0 to 0.0
|
SECONDARY outcome
Timeframe: Baseline, 2 monthsPopulation: Subjects still alive and able to tolerate cognitive testing at month 2 visit.
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.
Outcome measures
| Measure |
Placebo
n=9 Participants
Placebo : 100mg by mouth three times a day
|
Quinacrine
n=5 Participants
Quinacrine : 100mg by mouth three times a day
|
|---|---|---|
|
Change in Semantic Verbal Fluency (Naming Animals)
|
-3.2 number of words generated
Interval -9.0 to 2.0
|
-2.2 number of words generated
Interval -9.0 to 5.0
|
Adverse Events
Placebo Random Assignment
Quinacrine Random Assignment
Quinacrine Open-label
Serious adverse events
| Measure |
Placebo Random Assignment
n=28 participants at risk
Placebo : 100mg by mouth three times a day, Baseline-Month 2 = random assignment (n=28), Month 2+ = optional continuation of assigned drug (n=1).
|
Quinacrine Random Assignment
n=23 participants at risk
Quinacrine: 100mg by mouth three times a day. Baseline-Month 2 = random assignment (n=23), Month 2+ = optional continuation of assigned drug (n=1).
|
Quinacrine Open-label
n=24 participants at risk
Quinacrine: Month 2 until death = optional open-label Quinacrine 100mg by mouth three times a day
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/28 • 1 year
|
4.3%
1/23 • 1 year
|
0.00%
0/24 • 1 year
|
|
Nervous system disorders
Hemorrhage
|
3.6%
1/28 • 1 year
|
0.00%
0/23 • 1 year
|
4.2%
1/24 • 1 year
|
|
General disorders
Death
|
39.3%
11/28 • 1 year
|
43.5%
10/23 • 1 year
|
33.3%
8/24 • 1 year
|
|
Nervous system disorders
Seizure
|
0.00%
0/28 • 1 year
|
4.3%
1/23 • 1 year
|
0.00%
0/24 • 1 year
|
|
General disorders
Unclassified shaking
|
0.00%
0/28 • 1 year
|
4.3%
1/23 • 1 year
|
0.00%
0/24 • 1 year
|
|
Psychiatric disorders
Agitation
|
0.00%
0/28 • 1 year
|
0.00%
0/23 • 1 year
|
4.2%
1/24 • 1 year
|
|
Renal and urinary disorders
Elevated renal function labs
|
0.00%
0/28 • 1 year
|
0.00%
0/23 • 1 year
|
4.2%
1/24 • 1 year
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/28 • 1 year
|
0.00%
0/23 • 1 year
|
8.3%
2/24 • 1 year
|
|
Injury, poisoning and procedural complications
Post-LP infection
|
7.1%
2/28 • 1 year
|
0.00%
0/23 • 1 year
|
0.00%
0/24 • 1 year
|
|
Psychiatric disorders
Hallucinations
|
0.00%
0/28 • 1 year
|
0.00%
0/23 • 1 year
|
4.2%
1/24 • 1 year
|
|
Injury, poisoning and procedural complications
Post-LP headache
|
7.1%
2/28 • 1 year
|
0.00%
0/23 • 1 year
|
0.00%
0/24 • 1 year
|
|
Injury, poisoning and procedural complications
Post-LP Dizziness
|
7.1%
2/28 • 1 year
|
0.00%
0/23 • 1 year
|
0.00%
0/24 • 1 year
|
Other adverse events
| Measure |
Placebo Random Assignment
n=28 participants at risk
Placebo : 100mg by mouth three times a day, Baseline-Month 2 = random assignment (n=28), Month 2+ = optional continuation of assigned drug (n=1).
|
Quinacrine Random Assignment
n=23 participants at risk
Quinacrine: 100mg by mouth three times a day. Baseline-Month 2 = random assignment (n=23), Month 2+ = optional continuation of assigned drug (n=1).
|
Quinacrine Open-label
n=24 participants at risk
Quinacrine: Month 2 until death = optional open-label Quinacrine 100mg by mouth three times a day
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal abscess
|
0.00%
0/28 • 1 year
|
4.3%
1/23 • 1 year
|
0.00%
0/24 • 1 year
|
|
Psychiatric disorders
Agitation
|
3.6%
1/28 • 1 year
|
8.7%
2/23 • 1 year
|
8.3%
2/24 • 1 year
|
|
Hepatobiliary disorders
Elevated Liver Function Tests
|
0.00%
0/28 • 1 year
|
13.0%
3/23 • 1 year
|
50.0%
12/24 • 1 year
|
|
Gastrointestinal disorders
Diarrhea
|
3.6%
1/28 • 1 year
|
4.3%
1/23 • 1 year
|
20.8%
5/24 • 1 year
|
|
Infections and infestations
Urinary Tract Infection
|
10.7%
3/28 • 1 year
|
4.3%
1/23 • 1 year
|
4.2%
1/24 • 1 year
|
|
Blood and lymphatic system disorders
Potential thrombi
|
3.6%
1/28 • 1 year
|
0.00%
0/23 • 1 year
|
4.2%
1/24 • 1 year
|
|
Injury, poisoning and procedural complications
Post-LP complications
|
3.6%
1/28 • 1 year
|
0.00%
0/23 • 1 year
|
4.2%
1/24 • 1 year
|
|
Psychiatric disorders
Hallucination
|
7.1%
2/28 • 1 year
|
0.00%
0/23 • 1 year
|
0.00%
0/24 • 1 year
|
|
Blood and lymphatic system disorders
Pulmonary embolism
|
0.00%
0/28 • 1 year
|
4.3%
1/23 • 1 year
|
4.2%
1/24 • 1 year
|
|
Skin and subcutaneous tissue disorders
Rash
|
3.6%
1/28 • 1 year
|
0.00%
0/23 • 1 year
|
12.5%
3/24 • 1 year
|
|
Injury, poisoning and procedural complications
Hip Fracture
|
0.00%
0/28 • 1 year
|
0.00%
0/23 • 1 year
|
4.2%
1/24 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Elevated creatine kinase
|
0.00%
0/28 • 1 year
|
0.00%
0/23 • 1 year
|
4.2%
1/24 • 1 year
|
|
General disorders
Dizziness
|
0.00%
0/28 • 1 year
|
0.00%
0/23 • 1 year
|
4.2%
1/24 • 1 year
|
|
Nervous system disorders
Seizure
|
0.00%
0/28 • 1 year
|
0.00%
0/23 • 1 year
|
8.3%
2/24 • 1 year
|
|
Gastrointestinal disorders
Nausea
|
3.6%
1/28 • 1 year
|
4.3%
1/23 • 1 year
|
20.8%
5/24 • 1 year
|
|
Gastrointestinal disorders
Vomiting
|
3.6%
1/28 • 1 year
|
4.3%
1/23 • 1 year
|
20.8%
5/24 • 1 year
|
|
Blood and lymphatic system disorders
Leukopenia
|
3.6%
1/28 • 1 year
|
0.00%
0/23 • 1 year
|
0.00%
0/24 • 1 year
|
|
General disorders
Fever
|
3.6%
1/28 • 1 year
|
0.00%
0/23 • 1 year
|
0.00%
0/24 • 1 year
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place