Alzheimer's Disease
Conditions
Keywords
Alzheimer's, Dementia, Interferon beta-1a, Rebif
Brief summary
This was a 52-week, multicentric, phase II, pilot study conducted in 40 subjects with early-onset Alzheimer's disease (AD) to evaluate safety, tolerability and clinical efficacy of subcutaneous (sc) interferon (IFN) beta-1a \[Rebif® 22 microgram (mcg), three times per week (tiw)\] in the treatment of AD by comparing the neuropsychological performance changes into placebo and treatment arms from screening/baseline to 52 week.
Detailed description
Alzheimer's disease is characterized by progressive cognitive impairment resulting from neuronal loss. The primary pathological feature of the disease is the extracellular deposition of fibrillary amyloid and its compaction into senile plaques. The senile plaque is the focus of a complex cellular reaction involving the activation of both microglia and astrocytes adjacent to the amyloid plaque. In fact, microglias are the most abundant and prominent cellular components associated with these plaques. Plaque-associated microglia exhibits a reactive or activated phenotype. Through the acquisition of a reactive phenotype, microglia responds to various stimuli, as is evident by the increased expression of numerous cell-surface molecules, including major histocompatibility complex (MHC) class-II antigens and complement receptors. Traditionally, multiple sclerosis (MS) has been considered a demyelinating disease. Recent immunocytochemical studies suggest that MS may be more than a demyelinating disorder, and that even in early stages of the disease, MS pathological scenario envisages axonal damage. Interferons, the modern therapeutic strategies for the treatment of MS, are cytokines - proteins which lead to a network of signals within different cells. In the immune system, IFNs act at different levels. For example, IFNs increase the expression of MHC class II antigens and, thereby, facilitate the antigen-presenting process and the activation of lymphocytes. T-lymphocytes are important targets of IFN immunomodulation. In MS, it is believed that IFN beta suppresses the production of proinflammatory cytokines such as IFN-γ and TNF-α, and increases the production of immunosuppressive cytokines such as interleukin-4 (IL-4) and IL-10. Since the activation of microglia and astrocytes is common to both AD and MS, IFN beta could have therapeutic applications in the treatment of AD. Furthermore, recent studies have also found that through astrocyte production, IFNs promote the activation of nerve-growth factor. OBJECTIVES * To evaluate safety, tolerability and clinical efficacy of IFN beta-1a (Rebif® 22 mcg, tiw) in the treatment of AD In this study, subjects were randomized into two groups: the first group (treatment arm, n=20) received Rebif® 22 mcg tiw; the second group (placebo arm, n=20) received placebo. The treatment period was for 28 weeks and subjects were followed up to Week 52. Efficacy was determined by comparing neuropsychological performance changes into placebo and treatment arms from screening/baseline to Week 52. On Day 1 of the study treatment period, subjects received injection training and were administered the first dose of Rebif under the supervision of the clinical personnel by subcutaneous injection tiw at approximately the same time each day preferably in the late afternoon or evening. All subjects received 28 weeks of therapy and after 24 weeks from the therapy conclusion, a termination visit was conducted.
Interventions
DRUGInterferon beta-1a
Interferon (IFN) beta-1a \[Rebif® 22 microgram (mcg), three times per week (tiw)\] administered subcutaneously (sc)
DRUGPlacebo
The inactive substance (placebo) looks the same as Interferon beta-1a (Rebif®), and is given the same way
Sponsors
Merck Serono S.P.A., Italy
Merck KGaA, Darmstadt, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Subjects aged between 50 and 75 years * Subjects diagnosed with AD, according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) * Subjects with MMSE score of 20 to 26 (inclusive) * Subjects supervised by a caregiver * Subjects who have been given informed written consent and approval of the Local Ethical Committee
Exclusion criteria
* Subjects with constant use in the 3 months prior study enrolment of other drugs that can modify the course of the disease (e.g. statins, nonsteroidal anti-inflammatory drugs \[NSAIDs\] and steroids) or symptomatic cognitive treatments (e.g. cholinesterase inhibitors) * Subjects with modified Hachinski Ischemic Score ≥ 4 * Subjects who are unable to undergo neuropsychological evaluation (including analphabetism) * Subjects with significant liver (aspartate aminotransferase, alanine aminotransferase , alkaline phosphatase \> 2.0 times the upper limit of normal \[ULN\] of the local laboratory, or total bilirubin \> 1.5 times the ULN of the local laboratory), thyroid (according to clinical judgment) or hematological dysfunctions (e.g. leucocytes ≤ 2.0 \* 109/Liter \[L\]; platelets ≤ 100 \* 109/L; hemoglobin ≤ 12 gram/deciliter \[g/dL\] for women and ≤ 13 g/dL for men, serum albumin ≤ 3 g/dL) * Subjects with history (past or recurrent) of depression unresponsive to medication or past medical history of suicidal ideation * Subjects with severe cardiac disease (angina, congestive heart failure class 3-4 New York Heart Association \[NYHA\] Functional Classification , or severe arrhythmia) * Subjects with epilepsy * Subjects with concomitant use of hypnotic, anxiolytic, antidepressant, antipsychotic, anticholinergic * Subjects with known allergic reactions against IFNs or other components of the applied drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-Cog) Score | Baseline and Week 52 | ADAS: global rating scale created to evaluate both cognitive and functional aspects linked with disease progression. ADAS-Cog: subscale of ADAS which consists in a series of short tests aimed to evaluate possible cognitive impairment due to disease progression. It includes 11 items, testing word-finding difficulty, following commands, naming: objects and fingers, orientation, word recognition, recall of test instructions, constructions, ideational praxis, spoken language ability, comprehension of spoken language and word recall. Scores range from 0 (no impairment) to 70 (serious deficit). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mini Mental Status Examination (MMSE) Score | Baseline, Week 12, 28 and 52 | MMSE is a tool for screening cognitive decline associated with dementia. It is a brief examination intended to evaluate an adult participant's level of cognitive functioning. The test is performed in following areas: orientation in time and place, learning and immediate recall, mental control and concentration, short-term recall, naming ability, language expression, verbal comprehension, writing comprehension, writing ability and visual-spatial coordination. Scores range between 0 (maximum cognitive deficit) and 30 (no cognitive deficit). |
| Alzheimer's Disease Assessment Scale, Non-cognitive Subscale (ADAS-NonCog) Score | Baseline, Week 12, 28 and 52 | ADAS-NonCog is a subscale of ADAS aimed to evaluate the non-cognitive features such as mood state and behavioral changes. It takes about 10 minutes to be performed and includes 10 items: testing tearful, depressed mood, concentration/distractibility, uncooperative to testing, delusions, hallucinations, pacing, motor activity increase, tremors and appetite change. Scores range between 0 (excellent performance) and 35 (worst performance). |
| Instrumental Activities of Daily Living (IADL) Score | Baseline, Week 28 and 52 | IADL is used to evaluate participants with early-stage disease, both to assess level of disease and to determine participant's ability of self-care. IADL scale measures functional impact of emotional, cognitive, and physical impairments. It provides information about participants' compromising rate and care he might need. It includes 8 items: testing ability to use telephone, shopping, food preparation, housekeeping, laundry, mode of transportation, responsibility for own medication and ability to handle finances. Scores range between 0 (impairment) and 8 (full independence). |
| Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-Cog) Score | Week 12 and 28 | ADAS: global rating scale created to evaluate both cognitive and functional aspects linked with disease progression. ADAS-Cog: subscale of ADAS which consists in a series of short tests aimed to evaluate possible cognitive impairment due to disease progression. It includes 11 items, testing word-finding difficulty, following commands, naming: objects and fingers, orientation, word recognition, recall of test instructions, constructions, ideational praxis, spoken language ability, comprehension of spoken language and word recall. Scores range from 0 (no impairment) to 70 (serious deficit). |
| Clinician's Interview Based Impression of Change (CIBIC-PLUS) Score | Week 28 and 52 | CIBIC-PLUS: structured instrument based on comprehensive evaluation of 3 domains: participant cognition, behavior and functioning, including assessment of daily living activities. It includes 15 items and represents assessment of skilled clinician using validated scales based on the observation at interviews conducted separately with participant and caregiver familiar with behavior of participant. According to comparison between baseline and follow-up assessments, scores can range between 1 (markedly improved) and 7 (markedly worsened), with 4 indicating no change observed between two visits. |
| Geriatric Depression Scale (GDS) Score | Baseline, Week 28 and 52 | The GDS consists of 30 'yes' or 'no' items aimed to assess depression. One point is assigned to each answer and the cumulative score is rated on a scoring grid. Scores are grouped as follows: 0-9 'normal', 10-19 'mildly depressed', and 20-30 'severely depressed'. |
| Global Deterioration Scale Score | Baseline, Week 28 and 52 | Global deterioration scale includes seven different diagnostic stages ranging between no cognitive deterioration and very serious cognitive deterioration. It investigates the cognitive impairment. Scores range between 1 (no cognitive deterioration) and 7 (very severe cognitive decline). |
| Physical Self-Maintenance Scale (PSMS) Score | Baseline, Week 28 and 52 | PSMS designed as a disability measure for use in planning and evaluating treatment in elderly participants living in community or in institutions, is Guttman scale containing 6 items of self-care. The scale is based on theory that human behavior can be ordered in a hierarchy of complexity, within each category, a further hierarchy of complexity runs from basic to complex activities. It includes 6 items, testing the following areas: toilet use, eating, dressing, physical appearance, deambulation and bath. Scores range between 0 (excellent performance) and 30 (worst performance). |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rebif 22 Mcg Single dose of interferon beta-1a (Rebif) injection administered subcutaneously (sc) three times per week (tiw) at a dose of 4.4 microgram (mcg) for first 2 weeks followed by 11 mcg for next 2 weeks and finally 22 mcg for remaining 24 weeks (treatment period 28 weeks). | 23 |
| Placebo Single dose of matching placebo injection administered sc tiw at a dose of 4.4 mcg for first 2 weeks followed by 11 mcg for next 2 weeks and finally 22 mcg for remaining 24 weeks (treatment period of 28 weeks). | 19 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Rebif 22 Mcg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 63.00 years STANDARD_DEVIATION 9.08 | 64.58 years STANDARD_DEVIATION 6.41 | 63.71 years STANDARD_DEVIATION 7.87 |
| Sex: Female, Male Female | 15 Participants | 11 Participants | 26 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 23 | 5 / 19 |
| serious Total, serious adverse events | 0 / 23 | 0 / 19 |
Outcome results
Primary
Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-Cog) Score
ADAS: global rating scale created to evaluate both cognitive and functional aspects linked with disease progression. ADAS-Cog: subscale of ADAS which consists in a series of short tests aimed to evaluate possible cognitive impairment due to disease progression. It includes 11 items, testing word-finding difficulty, following commands, naming: objects and fingers, orientation, word recognition, recall of test instructions, constructions, ideational praxis, spoken language ability, comprehension of spoken language and word recall. Scores range from 0 (no impairment) to 70 (serious deficit).
Time frame: Baseline and Week 52
Population: Per protocol population included all participants who received treatments as scheduled and were followed up to week 52.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rebif 22 Mcg | Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-Cog) Score | Baseline | 18.63 units on a scale | Standard Deviation 7.86 |
| Rebif 22 Mcg | Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-Cog) Score | Week 52 | 20.66 units on a scale | Standard Deviation 9.55 |
| Placebo | Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-Cog) Score | Baseline | 19.81 units on a scale | Standard Deviation 6.15 |
| Placebo | Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-Cog) Score | Week 52 | 20.33 units on a scale | Standard Deviation 10.05 |
Comparison: For baseline: the difference between the two groups was analyzed using t-test.p-value: 0.64t-test, 2 sided
Comparison: For Week 52: the difference between the two groups was analyzed using t-test.p-value: 0.92t-test, 2 sided
Secondary
Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-Cog) Score
ADAS: global rating scale created to evaluate both cognitive and functional aspects linked with disease progression. ADAS-Cog: subscale of ADAS which consists in a series of short tests aimed to evaluate possible cognitive impairment due to disease progression. It includes 11 items, testing word-finding difficulty, following commands, naming: objects and fingers, orientation, word recognition, recall of test instructions, constructions, ideational praxis, spoken language ability, comprehension of spoken language and word recall. Scores range from 0 (no impairment) to 70 (serious deficit).
Time frame: Week 12 and 28
Population: Per protocol population included all participants who received treatments as scheduled and were followed up to week 52.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rebif 22 Mcg | Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-Cog) Score | Week 12 | 16.74 units on a scale | Standard Deviation 6.94 |
| Rebif 22 Mcg | Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-Cog) Score | Week 28 | 18.49 units on a scale | Standard Deviation 8.72 |
| Placebo | Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-Cog) Score | Week 12 | 17.97 units on a scale | Standard Deviation 6.28 |
| Placebo | Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-Cog) Score | Week 28 | 17.55 units on a scale | Standard Deviation 7.02 |
Comparison: For Week 12: the difference between the two groups was analyzed using t-test.p-value: 0.63t-test, 2 sided
Comparison: For Week 28: the difference between the two groups was analyzed using t-test.p-value: 0.74t-test, 2 sided
Secondary
Alzheimer's Disease Assessment Scale, Non-cognitive Subscale (ADAS-NonCog) Score
ADAS-NonCog is a subscale of ADAS aimed to evaluate the non-cognitive features such as mood state and behavioral changes. It takes about 10 minutes to be performed and includes 10 items: testing tearful, depressed mood, concentration/distractibility, uncooperative to testing, delusions, hallucinations, pacing, motor activity increase, tremors and appetite change. Scores range between 0 (excellent performance) and 35 (worst performance).
Time frame: Baseline, Week 12, 28 and 52
Population: Per protocol population included all participants who received treatments as scheduled and were followed up to week 52.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rebif 22 Mcg | Alzheimer's Disease Assessment Scale, Non-cognitive Subscale (ADAS-NonCog) Score | Baseline | 4.37 units on a scale | Standard Deviation 4.13 |
| Rebif 22 Mcg | Alzheimer's Disease Assessment Scale, Non-cognitive Subscale (ADAS-NonCog) Score | Week 12 | 3.53 units on a scale | Standard Deviation 3.24 |
| Rebif 22 Mcg | Alzheimer's Disease Assessment Scale, Non-cognitive Subscale (ADAS-NonCog) Score | Week 28 | 4.63 units on a scale | Standard Deviation 4.36 |
| Rebif 22 Mcg | Alzheimer's Disease Assessment Scale, Non-cognitive Subscale (ADAS-NonCog) Score | Week 52 | 5.47 units on a scale | Standard Deviation 5.17 |
| Placebo | Alzheimer's Disease Assessment Scale, Non-cognitive Subscale (ADAS-NonCog) Score | Week 52 | 7.20 units on a scale | Standard Deviation 6.97 |
| Placebo | Alzheimer's Disease Assessment Scale, Non-cognitive Subscale (ADAS-NonCog) Score | Baseline | 6.07 units on a scale | Standard Deviation 5.01 |
| Placebo | Alzheimer's Disease Assessment Scale, Non-cognitive Subscale (ADAS-NonCog) Score | Week 28 | 5.20 units on a scale | Standard Deviation 3.43 |
| Placebo | Alzheimer's Disease Assessment Scale, Non-cognitive Subscale (ADAS-NonCog) Score | Week 12 | 4.73 units on a scale | Standard Deviation 4.27 |
Comparison: For baseline: the difference between the two groups was analyzed using t-test.p-value: 0.29t-test, 2 sided
Comparison: For Week 12: the difference between the two groups was analyzed using t-test.p-value: 0.36t-test, 2 sided
Comparison: For Week 28: the difference between the two groups was analyzed using t-test.p-value: 0.68t-test, 2 sided
Comparison: For Week 52: the difference between the two groups was analyzed using t-test.p-value: 0.41t-test, 2 sided
Secondary
Clinician's Interview Based Impression of Change (CIBIC-PLUS) Score
CIBIC-PLUS: structured instrument based on comprehensive evaluation of 3 domains: participant cognition, behavior and functioning, including assessment of daily living activities. It includes 15 items and represents assessment of skilled clinician using validated scales based on the observation at interviews conducted separately with participant and caregiver familiar with behavior of participant. According to comparison between baseline and follow-up assessments, scores can range between 1 (markedly improved) and 7 (markedly worsened), with 4 indicating no change observed between two visits.
Time frame: Week 28 and 52
Population: Per protocol population included all participants who received treatments as scheduled and were followed up to week 52.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rebif 22 Mcg | Clinician's Interview Based Impression of Change (CIBIC-PLUS) Score | Week 28: CIBIC-PLUS Score 1 | 1 participants |
| Rebif 22 Mcg | Clinician's Interview Based Impression of Change (CIBIC-PLUS) Score | Week 28: CIBIC-PLUS Score 2 | 0 participants |
| Rebif 22 Mcg | Clinician's Interview Based Impression of Change (CIBIC-PLUS) Score | Week 28: CIBIC-PLUS Score 3 | 7 participants |
| Rebif 22 Mcg | Clinician's Interview Based Impression of Change (CIBIC-PLUS) Score | Week 28: CIBIC-PLUS Score 4 | 8 participants |
| Rebif 22 Mcg | Clinician's Interview Based Impression of Change (CIBIC-PLUS) Score | Week 28: CIBIC-PLUS Score 5 | 3 participants |
| Rebif 22 Mcg | Clinician's Interview Based Impression of Change (CIBIC-PLUS) Score | Week 28: CIBIC-PLUS Score 6 | 0 participants |
| Rebif 22 Mcg | Clinician's Interview Based Impression of Change (CIBIC-PLUS) Score | Week 28: CIBIC-PLUS Score 7 | 0 participants |
| Rebif 22 Mcg | Clinician's Interview Based Impression of Change (CIBIC-PLUS) Score | Week 52: CIBIC-PLUS Score 1 | 0 participants |
| Rebif 22 Mcg | Clinician's Interview Based Impression of Change (CIBIC-PLUS) Score | Week 52: CIBIC-PLUS Score 2 | 0 participants |
| Rebif 22 Mcg | Clinician's Interview Based Impression of Change (CIBIC-PLUS) Score | Week 52: CIBIC-PLUS Score 3 | 6 participants |
| Rebif 22 Mcg | Clinician's Interview Based Impression of Change (CIBIC-PLUS) Score | Week 52: CIBIC-PLUS Score 4 | 7 participants |
| Rebif 22 Mcg | Clinician's Interview Based Impression of Change (CIBIC-PLUS) Score | Week 52: CIBIC-PLUS Score 5 | 1 participants |
| Rebif 22 Mcg | Clinician's Interview Based Impression of Change (CIBIC-PLUS) Score | Week 52: CIBIC-PLUS Score 6 | 4 participants |
| Rebif 22 Mcg | Clinician's Interview Based Impression of Change (CIBIC-PLUS) Score | Week 52: CIBIC-PLUS Score 7 | 1 participants |
| Placebo | Clinician's Interview Based Impression of Change (CIBIC-PLUS) Score | Week 52: CIBIC-PLUS Score 4 | 4 participants |
| Placebo | Clinician's Interview Based Impression of Change (CIBIC-PLUS) Score | Week 28: CIBIC-PLUS Score 1 | 0 participants |
| Placebo | Clinician's Interview Based Impression of Change (CIBIC-PLUS) Score | Week 52: CIBIC-PLUS Score 1 | 0 participants |
| Placebo | Clinician's Interview Based Impression of Change (CIBIC-PLUS) Score | Week 28: CIBIC-PLUS Score 2 | 2 participants |
| Placebo | Clinician's Interview Based Impression of Change (CIBIC-PLUS) Score | Week 52: CIBIC-PLUS Score 6 | 3 participants |
| Placebo | Clinician's Interview Based Impression of Change (CIBIC-PLUS) Score | Week 28: CIBIC-PLUS Score 3 | 6 participants |
| Placebo | Clinician's Interview Based Impression of Change (CIBIC-PLUS) Score | Week 52: CIBIC-PLUS Score 2 | 2 participants |
| Placebo | Clinician's Interview Based Impression of Change (CIBIC-PLUS) Score | Week 28: CIBIC-PLUS Score 4 | 5 participants |
| Placebo | Clinician's Interview Based Impression of Change (CIBIC-PLUS) Score | Week 52: CIBIC-PLUS Score 5 | 4 participants |
| Placebo | Clinician's Interview Based Impression of Change (CIBIC-PLUS) Score | Week 28: CIBIC-PLUS Score 5 | 0 participants |
| Placebo | Clinician's Interview Based Impression of Change (CIBIC-PLUS) Score | Week 52: CIBIC-PLUS Score 3 | 2 participants |
| Placebo | Clinician's Interview Based Impression of Change (CIBIC-PLUS) Score | Week 28: CIBIC-PLUS Score 6 | 2 participants |
| Placebo | Clinician's Interview Based Impression of Change (CIBIC-PLUS) Score | Week 52: CIBIC-PLUS Score 7 | 0 participants |
| Placebo | Clinician's Interview Based Impression of Change (CIBIC-PLUS) Score | Week 28: CIBIC-PLUS Score 7 | 0 participants |
Secondary
Geriatric Depression Scale (GDS) Score
The GDS consists of 30 'yes' or 'no' items aimed to assess depression. One point is assigned to each answer and the cumulative score is rated on a scoring grid. Scores are grouped as follows: 0-9 'normal', 10-19 'mildly depressed', and 20-30 'severely depressed'.
Time frame: Baseline, Week 28 and 52
Population: Per protocol population included all participants who received treatments as scheduled and were followed up to week 52.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rebif 22 Mcg | Geriatric Depression Scale (GDS) Score | Baseline | 10.11 units on a scale | Standard Deviation 6.13 |
| Rebif 22 Mcg | Geriatric Depression Scale (GDS) Score | Week 28 | 9.68 units on a scale | Standard Deviation 5.74 |
| Rebif 22 Mcg | Geriatric Depression Scale (GDS) Score | Week 52 | 10.79 units on a scale | Standard Deviation 5.93 |
| Placebo | Geriatric Depression Scale (GDS) Score | Baseline | 10.67 units on a scale | Standard Deviation 6.53 |
| Placebo | Geriatric Depression Scale (GDS) Score | Week 28 | 9.07 units on a scale | Standard Deviation 4.32 |
| Placebo | Geriatric Depression Scale (GDS) Score | Week 52 | 7.50 units on a scale | Standard Deviation 5.56 |
Comparison: For baseline: the difference between the two groups was analyzed using t-test.p-value: 0.8t-test, 2 sided
Comparison: For Week 28: the difference between the two groups was analyzed using t-test.p-value: 0.74t-test, 2 sided
Comparison: For Week 52: the difference between the two groups was analyzed using t-test.p-value: 0.12t-test, 2 sided
Secondary
Global Deterioration Scale Score
Global deterioration scale includes seven different diagnostic stages ranging between no cognitive deterioration and very serious cognitive deterioration. It investigates the cognitive impairment. Scores range between 1 (no cognitive deterioration) and 7 (very severe cognitive decline).
Time frame: Baseline, Week 28 and 52
Population: Per protocol population included all participants who received treatments as scheduled and were followed up to week 52.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rebif 22 Mcg | Global Deterioration Scale Score | Baseline | 3.00 units on a scale | Standard Deviation 0.47 |
| Rebif 22 Mcg | Global Deterioration Scale Score | Week 28 | 3.05 units on a scale | Standard Deviation 0.78 |
| Rebif 22 Mcg | Global Deterioration Scale Score | Week 52 | 3.26 units on a scale | Standard Deviation 0.81 |
| Placebo | Global Deterioration Scale Score | Baseline | 2.87 units on a scale | Standard Deviation 0.74 |
| Placebo | Global Deterioration Scale Score | Week 28 | 3.00 units on a scale | Standard Deviation 0.93 |
| Placebo | Global Deterioration Scale Score | Week 52 | 3.20 units on a scale | Standard Deviation 1.08 |
Comparison: For baseline: the difference between the two groups was analyzed using t-test.p-value: 0.53t-test, 2 sided
Comparison: For Week 28: the difference between the two groups was analyzed using t-test.p-value: 0.85t-test, 2 sided
Comparison: For Week 52: the difference between the two groups was analyzed using t-test.p-value: 0.85t-test, 2 sided
Secondary
Instrumental Activities of Daily Living (IADL) Score
IADL is used to evaluate participants with early-stage disease, both to assess level of disease and to determine participant's ability of self-care. IADL scale measures functional impact of emotional, cognitive, and physical impairments. It provides information about participants' compromising rate and care he might need. It includes 8 items: testing ability to use telephone, shopping, food preparation, housekeeping, laundry, mode of transportation, responsibility for own medication and ability to handle finances. Scores range between 0 (impairment) and 8 (full independence).
Time frame: Baseline, Week 28 and 52
Population: Per protocol population included all participants who received treatments as scheduled and were followed up to week 52.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rebif 22 Mcg | Instrumental Activities of Daily Living (IADL) Score | Baseline | 6.11 units on a scale | Standard Deviation 1.45 |
| Rebif 22 Mcg | Instrumental Activities of Daily Living (IADL) Score | Week 28 | 5.84 units on a scale | Standard Deviation 1.17 |
| Rebif 22 Mcg | Instrumental Activities of Daily Living (IADL) Score | Week 52 | 4.89 units on a scale | Standard Deviation 1.85 |
| Placebo | Instrumental Activities of Daily Living (IADL) Score | Baseline | 6.20 units on a scale | Standard Deviation 1.57 |
| Placebo | Instrumental Activities of Daily Living (IADL) Score | Week 28 | 5.60 units on a scale | Standard Deviation 1.68 |
| Placebo | Instrumental Activities of Daily Living (IADL) Score | Week 52 | 5.67 units on a scale | Standard Deviation 1.63 |
Comparison: For baseline: the difference between the two groups was analyzed using t-test.p-value: 0.86t-test, 2 sided
Comparison: For Week 28: the difference between the two groups was analyzed using t-test.p-value: 0.62t-test, 2 sided
Comparison: For Week 52: the difference between the two groups was analyzed using t-test.p-value: 0.21t-test, 2 sided
Secondary
Mini Mental Status Examination (MMSE) Score
MMSE is a tool for screening cognitive decline associated with dementia. It is a brief examination intended to evaluate an adult participant's level of cognitive functioning. The test is performed in following areas: orientation in time and place, learning and immediate recall, mental control and concentration, short-term recall, naming ability, language expression, verbal comprehension, writing comprehension, writing ability and visual-spatial coordination. Scores range between 0 (maximum cognitive deficit) and 30 (no cognitive deficit).
Time frame: Baseline, Week 12, 28 and 52
Population: Per protocol population included all participants who received treatments as scheduled and were followed up to week 52.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rebif 22 Mcg | Mini Mental Status Examination (MMSE) Score | Baseline | 23.46 units on a scale | Standard Deviation 2.14 |
| Rebif 22 Mcg | Mini Mental Status Examination (MMSE) Score | Week 12 | 24.50 units on a scale | Standard Deviation 3.22 |
| Rebif 22 Mcg | Mini Mental Status Examination (MMSE) Score | Week 28 | 24.25 units on a scale | Standard Deviation 3.37 |
| Rebif 22 Mcg | Mini Mental Status Examination (MMSE) Score | Week 52 | 22.43 units on a scale | Standard Deviation 5.33 |
| Placebo | Mini Mental Status Examination (MMSE) Score | Week 52 | 21.98 units on a scale | Standard Deviation 5.32 |
| Placebo | Mini Mental Status Examination (MMSE) Score | Baseline | 22.93 units on a scale | Standard Deviation 1.79 |
| Placebo | Mini Mental Status Examination (MMSE) Score | Week 28 | 23.66 units on a scale | Standard Deviation 4.92 |
| Placebo | Mini Mental Status Examination (MMSE) Score | Week 12 | 24.66 units on a scale | Standard Deviation 3.14 |
Comparison: For baseline: the difference between the two groups was analyzed using t-test.p-value: 0.45t-test, 2 sided
Comparison: For Week 12: the difference between the two groups was analyzed using t-test.p-value: 0.88t-test, 2 sided
Comparison: For Week 28: the difference between the two groups was analyzed using t-test.p-value: 0.68t-test, 2 sided
Comparison: For Week 52: the difference between the two groups was analyzed using t-test.p-value: 0.81t-test, 2 sided
Secondary
Physical Self-Maintenance Scale (PSMS) Score
PSMS designed as a disability measure for use in planning and evaluating treatment in elderly participants living in community or in institutions, is Guttman scale containing 6 items of self-care. The scale is based on theory that human behavior can be ordered in a hierarchy of complexity, within each category, a further hierarchy of complexity runs from basic to complex activities. It includes 6 items, testing the following areas: toilet use, eating, dressing, physical appearance, deambulation and bath. Scores range between 0 (excellent performance) and 30 (worst performance).
Time frame: Baseline, Week 28 and 52
Population: Per protocol population included all participants who received treatments as scheduled and were followed up to week 52.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rebif 22 Mcg | Physical Self-Maintenance Scale (PSMS) Score | Baseline | 6.42 units on a scale | Standard Deviation 1.02 |
| Rebif 22 Mcg | Physical Self-Maintenance Scale (PSMS) Score | Week 28 | 6.74 units on a scale | Standard Deviation 1.37 |
| Rebif 22 Mcg | Physical Self-Maintenance Scale (PSMS) Score | Week 52 | 7.79 units on a scale | Standard Deviation 3.34 |
| Placebo | Physical Self-Maintenance Scale (PSMS) Score | Baseline | 6.40 units on a scale | Standard Deviation 0.91 |
| Placebo | Physical Self-Maintenance Scale (PSMS) Score | Week 28 | 7.00 units on a scale | Standard Deviation 2.65 |
| Placebo | Physical Self-Maintenance Scale (PSMS) Score | Week 52 | 6.87 units on a scale | Standard Deviation 1.68 |
Comparison: For baseline: the difference between the two groups was analyzed using t-test.p-value: 0.95t-test, 2 sided
Comparison: For Week 28: the difference between the two groups was analyzed using t-test.p-value: 0.73t-test, 2 sided
Comparison: For Week 52: the difference between the two groups was analyzed using t-test.p-value: 0.3t-test, 2 sided