A Pilot Trial of Interferon Beta-1a in Alzheimer's Disease (REAL)
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
|Official Title:||Pilot Trial of Interferon Beta-1a in Alzheimer's Disease|
- Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-Cog) Score [ Time Frame: 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).
- Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-Cog) Score [ Time Frame: 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).
- Mini Mental Status Examination (MMSE) Score [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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).
- Physical Self-Maintenance Scale (PSMS) Score [ Time Frame: 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).
- Clinician's Interview Based Impression of Change (CIBIC-PLUS) Score [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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).
|Study Start Date:||November 2004|
|Study Completion Date:||May 2008|
|Primary Completion Date:||May 2008 (Final data collection date for primary outcome measure)|
Experimental: Treatment arm - Rebif®
Subjets in this arm received interferon beta-1a (Rebif® 22 mcg tiw)
Drug: Interferon beta-1a
Interferon (IFN) beta-1a [Rebif® 22 microgram (mcg), three times per week (tiw)] administered subcutaneously (sc)
Other Name: Rebif®
Placebo Comparator: Placebo arm
Subjects in this arm received placebo
The inactive substance (placebo) looks the same as Interferon beta-1a (Rebif®), and is given the same way
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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01075763
|U.VA. Neurologia - Azienda Ospedaliera Garibaldi Nesina|
|Catania, CT, Italy, 95122|
|Study Director:||Andrea Paolillo, MD, PhD||Merck Serono S.P.A., Italy|