Dataset Information

Mecasin treatment in patients with amyotrophic lateral sclerosis: study protocol for a randomized controlled trial.

ABSTRACT:

Background

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes paralysis of limb, swallowing, and breathing muscles. Riluzole, the Food and Drug Administration-approved drug for ALS, provides minimal benefit, prolonging patient life by only 2-3 months. Previous studies have found a neuro-protective and anti-neuroinflammatory effect of Mecasin, with retrospective studies providing suggestive evidence for a beneficial effect of Mecasin. The aim of this study was to develop a protocol to determine the proper dosage of Mecasin.

Methods

This is a phase II-A, multi-center, randomized study with three arms. Thirty-six patients with ALS will be randomly assigned to one of three groups, each receiving the standard treatment with 100 mg of riluzole in addition to one of 1.6 g of Mecasin, 2.4 g of Mecasin, or a placebo. The Primary outcome is the Korean version of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised result after 12 weeks of treatment. Secondary outcomes include results of the Short Form Health Survey-8, Medical Research Council Scale, Visual Analogue Scale for Pain, Hamilton Rating Scale for Depression, Fatigue Severity Scale, Patient Global Impression of Change, pulmonary function test, forced expiratory volume in 1 s and its ratio to forced vital capacity, creatine kinase, and body weight. The frequencies of total adverse events and serious adverse events will be described and documented. The trial protocol has been approved by the Institutional Review Board of the Wonkwang University Gwangju and Sanbon Hospital (2016-5-4 and 2016-34-01, respectively). An Investigational New Drug status (30731) was granted by the Korea Food and Drug Administration.

Discussion

This trial will aim to identify the optimal dosage of Mecasin. Additionally, it will test the efficacy and safety of Mecasin in conjunction with standard treatment, riluzole, for alleviating the functional decline in patients with ALS.

Trial registration

Korean National Clinical Trial Registry CRIS; KCT0001984 . Registered on 28 July 2016.

SUBMITTER: Kim S

PROVIDER: S-EPMC5899359 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Mecasin treatment in patients with amyotrophic lateral sclerosis: study protocol for a randomized controlled trial.

Kim Sungha S Kim Jae Kyoun JK Son Mi Ju MJ Kim Dongwoung D Song Bongkeun B Son Ilhong I Kang Hyung Won HW Lee Jongdeok J Kim Sungchul S

Trials 20180413 1

<h4>Background</h4>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes paralysis of limb, swallowing, and breathing muscles. Riluzole, the Food and Drug Administration-approved drug for ALS, provides minimal benefit, prolonging patient life by only 2-3 months. Previous studies have found a neuro-protective and anti-neuroinflammatory effect of Mecasin, with retrospective studies providing suggestive evidence for a beneficial effect of Mecasin. The aim of this stud ...[more]

PMID: 29653550

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Project description:Background and Rationale: Among the key players in the pathogenesis of Amyotrophic Lateral Sclerosis (ALS), microglia and T regulatory lymphocytes (Treg) are candidate cells for modifying the course of the disease. The gut microbiota (GM) acts by shaping immune tolerance and regulating the Treg number and suppressive function, besides circulating neuropeptides, and other immune cells that play in concert through the gut-brain axis. Previous mouse models have shown an altered enteric flora in early stage ALS, pointing to a possible GM role in ALS pathogenesis. Fecal Microbial Transplantation (FMT) is a well-known therapeutic intervention used to re-establish the proper microenvironment and to modulate enteric and systemic immunity. Methods: We are going to perform a multicenter randomized double-blind clinical trial employing FMT as a therapeutic intervention for ALS patients (NCT0376632). Forty-two ALS patients, at an early stage, will be enrolled with a 2:1 allocation ratio (28 FMT-treated patients vs. 14 controls). Study duration will be 12 months per patient. Three endoscopic procedures for intestinal biopsies in FMT and control groups are predicted at baseline, month 6 and month 12; at baseline and at month 6 fresh feces from healthy donors will be infused at patients in the intervention arm. The primary outcome is a significant change in Treg number between FMT-treated patients and control arm from baseline to month 6. Secondary outcomes include specific biological aims, involving in-depth analysis of immune cells and inflammatory status changes, central and peripheral biomarkers of ALS, besides comprehensive analysis of the gut, saliva and fecal microbiota. Other secondary aims include validated clinical outcomes of ALS (survival, forced vital capacity, and modifications in ALSFRS-R), besides safety and quality of life. Expected Results: We await FMT to increase Treg number and suppressive functionality, switching the immune system surrounding motorneurons to an anti-inflammatory, neuroprotective status. Extensive analysis on immune cell populations, cytokines levels, and microbiota (gut, fecal and saliva) will shed light on early processes possibly leading the degenerative ALS course. Conclusions: This is the first trial with FMT as a potential intervention to modify immunological response to ALS and disease progression at an early stage.

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Project description:INTRODUCTION:Amyotrophic lateral sclerosis (ALS) is a rapid and fatal motor disease marked by progressive physical impairment due to muscle weakness and wasting. It is multidimensional with many patients presenting with cognitive and/or behavioural impairment. Caregivers of patients with ALS, commonly non-paid immediate family members, often take primary responsibility for the complex care needs of patients in non-medicalised setting, and many as a consequence experience caregiver burden, anxiety, and/or depression. METHODS AND ANALYSIS:This randomised controlled trial (RCT) will use randomisation to allocate n=75 caregivers of patients with ALS from the national ALS clinic into three groups with an equal distribution. The RCT consists of two intervention groups and a wait list control (treatment as usual [TAU]) group. The intervention arms of the trial consist of a 'mindfulness-based stress reduction' and 'building better caregivers' manualised group-based intervention, with 9 and 6 weekly sessions, respectively. The TAU group will have access to intervention at the end of the trial period. Primary outcomes are self-report questionnaires on anxiety and depression symptoms, with caregiver burden and quality of life considered secondary outcomes. Assessment will commence at baseline, immediately following the intervention period, and after a period of 12 weeks to assess the effectiveness and efficacy of participating in an intervention. Patient cognitive and behavioural data will also be considered. Means of treatment and control groups at Time 0 and 1 will be analysed using mixed model multivariate analysis of variance followed by analysis of variance, and treatment effect-sizes will be calculated. This RCT protocol is pre-results and has been registered with an international database resulting in an International Standard Randomised Controlled Trials Number (ISRCTN53226941). ETHICS AND DISSEMINATION:Ethics approval was obtained from the Beaumont Hospital Medical Research Ethics Committee. Results of the main trial will be submitted for publication in a peer-reviewed journal.

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Dataset Information

Mecasin treatment in patients with amyotrophic lateral sclerosis: study protocol for a randomized controlled trial.

Background

Methods

Discussion

Trial registration

Publications

Mecasin treatment in patients with amyotrophic lateral sclerosis: study protocol for a randomized controlled trial.

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