A Pilot Trial of Interferon Beta-1a in Alzheimer's Disease
Condition: Alzheimer's Disease
MeSH terms: Alzheimer Disease
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Interferon beta-1a; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Interferon (IFN) beta-1a [Rebif® 22 microgram (mcg), three times per week (tiw)] administered subcutaneously (sc); The inactive substance (placebo) looks the same as Interferon beta-1a (Rebif®), and is given the same way
Other intervention name(s): Rebif®
Intervention MeSH terms: Interferons; Interferon-beta; Interferon beta-1a
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Alzheimer's; Dementia; Interferon beta-1a; Rebif