Cognitive Impairment, Multiple Sclerosis
Conditions
Keywords
Multiple Sclerosis, Cognition, Rivastigmine, Patch
Brief summary
This study evaluated the efficacy and safety of 10 cm² rivastigmine patch vs. placebo in cognitively impaired Multiple Sclerosis (MS) patients. Primary objective was the assessment of cognition by the Selective Reminding Test (SRT) -a subtest of the brief repeatable battery (BRB) - after titration of 4 weeks and maintenance of 12 weeks. This double-blind period was followed by a 52-week open-label treatment phase to assess long-term safety of rivastigmine patch in these patients.
Interventions
Transdermalapplication of one 5 cm² patch, followed by an increase to the target dose of 10 cm² patch size. All patches are round, beige in color.
DRUGPlacebo
Transdermal application of one 5 cm² patch, followed by an increase to the target dose of 10 cm² patch size. Matching the size, shape and color of rivastigmine patches.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Written informed consent to participate in the trial 2. Males and females between 18 and 55 years of age; 3. Definite diagnosis of multiple sclerosis as defined by 2005 revised McDonald criteria 4. MS-subtype: Clinical isolated syndrome (CIS), Relapsing Remitting Multiple Sclerosis (RRMS), Secondary progressive Multiple Sclerosis (SPMS); 5. Cognitive Impairment 6. Sufficient education to read, write and communicate comprehensibly
Exclusion criteria
1. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer 2. Women who are pregnant or breast feeding or who are menstruating and capable of becoming pregnant and not practicing a medically approved method of contraception 3. With a physical or sensory disability that can subjectively prevent the patient from completing all study requirements 4. Patients suffering any other type of concomitant psychiatric and/or neurological disorder other than MS which is known to affect cognition (e.g. severe depressive symptoms, cerebrovascular diseases, epilepsy). 5. Patients suffering an acute relapse of MS in the previous 30 days (treated or not with intravenous or oral glucocorticoid regimens) prior to baseline. 6. With a history or current problem of drug-addiction and/or alcohol abuse. 7. Known or 'new' diagnosis of diabetes mellitus (if screening blood glucose is suspicious for diabetes \[≥126 mg/dL or ≥7 mmol/L if fasting and ≥200 mg/dL or 11.1 mmol/L if random testing\] a patient should be further evaluated for diabetes mellitus) 8. With a history of severe or moderate-severe cranioencephalic trauma. 9. History or presence of any intolerance or contraindication for the application of rivastigmine (or for drugs with similar chemical structures) as listed in the current Investigator's Brochure and/or SPC, i.e. severe liver insufficiency, pancreatitis, gastric ulcer, convulsions. 10. With a history in the past year or a current diagnosis of cerebrovascular disease (for instance, stroke, transient ischemic events, aneurysms). 11. Severe depressive symptoms indicated by a score of more than ≥ 14 on the MADRS at screening 12. History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 16 in Total Recall on the Selective Reminding Test (SRT) in the Intent to Treat (ITT) Population | After 16 weeks of treatment | The Selective Reminding Test(SRT) is a test to assess verbal learning and memory. During the administration of the SRT only the examiner and the patient should be in the testing room. A list of twelve words is read aloud by the examiner at a rate of one word per two seconds. The patient is asked to recall all twelve words. Only the words that are missed on the preceding trial are given in the consecutive trial. The total score represents a sum score of 6 trials, therefore the range is from 0-72. The lower the value the worse the outcome. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rivastigmine 5 and 10 cm² patch sizes (4,6mg/24h or 9,5mg/24h) of rivastigmine, | 43 |
| Placebo Matching the size, shape and color of rivastigmine patches. | 38 |
| Total | 81 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative problems | 1 | 1 |
| Overall Study | Adverse Event | 8 | 3 |
| Overall Study | Condition no longer requires drug | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Rivastigmine | Placebo | Total |
|---|---|---|---|
| Age Continuous | 44.6 years STANDARD_DEVIATION 9.4 | 44.0 years STANDARD_DEVIATION 7.3 | 44.3 years STANDARD_DEVIATION 8.5 |
| Sex: Female, Male Female | 23 Participants | 20 Participants | 43 Participants |
| Sex: Female, Male Male | 20 Participants | 18 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 48 / 86 | 25 / 45 | 23 / 41 |
| serious Total, serious adverse events | 6 / 86 | 2 / 45 | 4 / 41 |
Outcome results
Primary
Change From Baseline to Week 16 in Total Recall on the Selective Reminding Test (SRT) in the Intent to Treat (ITT) Population
The Selective Reminding Test(SRT) is a test to assess verbal learning and memory. During the administration of the SRT only the examiner and the patient should be in the testing room. A list of twelve words is read aloud by the examiner at a rate of one word per two seconds. The patient is asked to recall all twelve words. Only the words that are missed on the preceding trial are given in the consecutive trial. The total score represents a sum score of 6 trials, therefore the range is from 0-72. The lower the value the worse the outcome.
Time frame: After 16 weeks of treatment
Population: Due to low enrollment numbers study did not achieve the anticipated 80% power.