Advertisement

Topics

A Pilot Trial of Interferon Beta-1a in Alzheimer's Disease

2014-08-27 03:15:37 | BioPortfolio

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 interferon (IFN) beta-1a [Rebif 22 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.

Description

Alzheimer's disease is characterised 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, microglia are the most abundant and prominent cellular components associated with these plaques. Plaque-associated microglia exhibit 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 are the modern therapeutic strategies for the treatment of MS which 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 randomised 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 study Day 1 of the 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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Conditions

Alzheimer's Disease

Intervention

Interferon beta-1a, Placebo

Location

U.VA. Neurologia - Azienda Ospedaliera Garibaldi Nesina
Catania
CT
Italy
95122

Status

Completed

Source

Merck KGaA

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:15:37-0400

Clinical Trials [2296 Associated Clinical Trials listed on BioPortfolio]

Phase II Cladribine Add-on to Inteferon-beta (IFN-b) Therapy in MS Subjects With Active Disease

The goal of this study is to evaluate the safety, tolerability and effectiveness of oral cladribine when taken in combination with Interferon-beta therapy for the treatment of MS. This st...

A Multicentre Phase III Study of Interferon-Beta-1a for the Treatment of Chronic Hepatitis C in Asian Patients

The main objective of this study is to establish interferon-beta-1a as the treatment of choice for chronic hepatitis C with better efficacy & safety profiles in monotherapy or combination ...

Statin Effects on Beta-Amyloid and Cerebral Perfusion in Adults at Risk for Alzheimer's Disease

The purpose of the research is to see how simvastatin affects a substance in the body called beta-amyloid. Beta-amyloid is found in the brain and in the liquid around the brain and spinal ...

Betaferon/ Betaseron (Interferon Beta-1b) in Patients With Chronic Viral Cardiomyopathy

Chronic viral cardiomyopathy is a disease where the cardiac muscle is attacked by a virus and this may result in a reduction in the output of the heart (pump function) thereby causing comp...

BEYOND Follow-up: Betaferon®/Betaseron® Efficacy Yielding Outcomes of a New Dose

The BEYOND Follow-Up study will give patients who participated in the preceding BEYOND study the opportunity to continue treatment with the 500µg dose of interferon beta (IFNB) 1b and wil...

PubMed Articles [17304 Associated PubMed Articles listed on BioPortfolio]

Decreased Parietal Beta Power as a Sign of Disease Progression in Patients with Mild Cognitive Impairment.

Electroencephalography (EEG) power has previously been used to compare mild cognitive impairment (MCI) patients who progress to Alzheimer's disease (pMCI) with patients with MCI who remain stable (sMC...

Alzheimer's disease pathology propagation by exosomes containing toxic amyloid-beta oligomers.

The gradual deterioration of cognitive functions in Alzheimer's disease is paralleled by a hierarchical progression of amyloid-beta and tau brain pathology. Recent findings indicate that toxic oligome...

Randomized Trial of Verubecestat for Mild-to-Moderate Alzheimer's Disease.

Alzheimer's disease is characterized by the deposition of amyloid-beta (Aβ) plaques in the brain. Aβ is produced from the sequential cleavage of amyloid precursor protein by β-site amyloid precurso...

Matching-adjusted comparisons demonstrate better clinical outcomes with SC peginterferon beta-1a every two weeks than with SC interferon beta-1a three times per week.

Subcutaneous (SC) peginterferon beta-1a and SC interferon beta-1a (IFN beta-1a) have demonstrated efficacy in treating relapsing-remitting multiple sclerosis (RRMS) but have never been compared in dir...

Imaging correlations of tau, amyloid, metabolism, and atrophy in typical and atypical Alzheimer's disease.

Neuroimaging modalities can measure different aspects of the disease process in Alzheimer's disease, although the relationship between these modalities is unclear.

Medical and Biotech [MESH] Definitions

Interferon secreted by leukocytes, fibroblasts, or lymphoblasts in response to viruses or interferon inducers other than mitogens, antigens, or allo-antigens. They include alpha- and beta-interferons (INTERFERON-ALPHA and INTERFERON-BETA).

A precursor to the AMYLOID BETA-PROTEIN (beta/A4). Alterations in the expression of the amyloid beta-protein precursor (ABPP) gene, located on chromosome 21, plays a role in the development of the neuropathology common to both ALZHEIMER DISEASE and DOWN SYNDROME. ABPP is associated with the extensive extracellular matrix secreted by neuronal cells. Upon cleavage, this precursor produces three proteins of varying amino acid lengths: 695, 751, and 770. The beta/A4 (695 amino acids) or beta-amyloid protein is the principal component of the extracellular amyloid in senile plaques found in ALZHEIMER DISEASE; DOWN SYNDROME and, to a limited extent, in normal aging.

A ubiquitously expressed heterodimeric receptor that is specific for both INTERFERON-ALPHA and INTERFERON-BETA. It is composed of two subunits referred to as IFNAR1 and IFNAR2. The IFNAR2 subunit is believed to serve as the ligand-binding chain; however both chains are required for signal transduction. The interferon alpha-beta receptor signals through the action of JANUS KINASES such as the TYK2 KINASE.

An interferon regulatory factor that binds upstream TRANSCRIPTIONAL REGULATORY ELEMENTS in the GENES for INTERFERON-ALPHA and INTERFERON-BETA. It functions as a transcriptional activator for the INTERFERON TYPE I genes.

An interferon beta-1 subtype that has a methionine at position 1, a cysteine at position 17, and is glycosylated at position 80. It functions as an ANTI-VIRAL AGENT and IMMUNOMODULATOR and is used to manage the symptoms of RELAPSING-REMITTING MULTIPLE SCLEROSIS.

More From BioPortfolio on "A Pilot Trial of Interferon Beta-1a in Alzheimer's Disease"

Advertisement
Quick Search
Advertisement
Advertisement

 

Relevant Topics

Clincial Trials
In a clinical trial or interventional study, participants receive specific interventions according to the research plan or protocol created by the investigators. These interventions may be medical products, such as drugs or devices; procedures; or change...

Psychiatry
Psychiatry is the study of mental disorders and their diagnosis, management and prevention.  Conditions include schizophrenia, severe depression and panic disorders among others. There are pharmaceutical treatments as well as other therapies to help...


Searches Linking to this Trial