Clinical Trial: Dimethyl Fumarate Treatment of Primary Progressive Multiple Sclerosis
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: Dimethyl Fumarate Treatment of Primary Progressive Multiple Sclerosis
Brief Summary:
This study aims to evaluate safety and efficacy of dimethyl fumarate treatment in patients with primary progressive multiple sclerosis (PPMS).
Half of the patients will receive dimethyl fumarate and the other half will receive placebo.
Detailed Summary:
Multiple sclerosis (MS) is a chronic, inflammatory disease of the central nervous system and is presumed to be caused by T cell-mediated autoimmune processes. PPMS has no registered treatment options only symptomatic treatment exists. Progressive forms of MS are characterized clinically by gradual symptom development with or without superimposed relapses.
Fumarates have long been known to have disease-attenuating effects in psoriasis. They have been in routine use in dermatology in Germany for several decades. Dimethyl fumarate has the interesting property of combining immunological effects, at least partly mediated by interference with nuclear factor kappa B and other transcription factors, and also anti-oxidative and neuroprotective effects mediated by activation of the transcription factor Nuclear factor (erythroid-derived 2)-Related Factor 2 (NRF2). Dimethyl fumarate is currently approved for treatment of relapsing-remitting MS by the European medicines Agency in a dose of 240 mg twice per day.
Neurofilament light chain (NFL) is a treatment responsive biomarker of neuronal and axonal death when appearing in the cerebrospinal fluid (CSF) and it has been associated with long-term prognosis in MS. The concentration is often elevated in progressive MS patients. Treatment effect is measured by measuring changes in neurofilament light chain concentration over the course of 48 weeks of treatment with either active drug or placebo.
Sponsor: Rigshospitalet, Denmark
Current Primary Outcome: Neuro filament light chain [ Time Frame: 0-48 weeks ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Expanded Disability Status Scale (EDSS) [ Time Frame: 0-48 weeks ]Is assessed by neurostatus 03/09 by either the primary investigator or another medical doctor to whom the task has been delegated. The evaluation is performed at baseline and at week 48 and change is recorded.
- Timed 25-Foot Walk (T25FW) [ Time Frame: 0-48 weeks ]Is assessed by a trained research nurse, the primary investigator or another medical doctor to whom the task has been delegated. The test is performed at baseline and at week 48 and change is recorded.
- Nine hole peg test (9HPT) [ Time Frame: 0-48 weeks ]Is assessed by a trained research nurse, the primary investigator or another medical doctor to whom the task has been delegated. The test is performed at baseline and at week 48 and change is recorded.
- Symbol digit modalities test (SDMT) [ Time Frame: 0-48 weeks ]Is assessed by a trained research nurse, the primary investigator or another medical doctor to whom the task has been delegated. The test is performed at baseline and at week 48 and change is recorded.
- Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) [ Time Frame: 0-48 weeks ]Is assessed by a trained research nurse, the primary investigator or another medical doctor to whom the task has been delegated. The test is performed at baseline and at week 48 and change is recorded.
- Low contrast visual acuity (LCVA) [ Time Frame: 0-48 weeks ]Is assessed by a trained research nurse, the primary investigator or another medical doctor to whom the task has been delegated. The test is performed at baseline and at week 48 and change is recorded.
- Urinary distress inventory (UDI) [ Time Frame: 0-48 weeks ]Is assessed by questionnaire. The questionnaire is handed out at baseline and at week 48 and change is recorded.
- Fatigue Scale for Motor and Cognitive Functions (FSMC) [ Time Frame: 0-48 weeks ]Is assessed by questionnaire. The questionnaire is handed out at baseline and at week 48 and change is recorded.
- Multiple Sclerosis Impact Scale 29 (MSIS-29) [ Time Frame: 0-48 weeks ]Is assessed by questionnaire. The questionnaire is handed out at baseline and at week 48 and change is recorded.
- Cerebrospinal fluid cell count [ Time Frame: 0-48 weeks ]Is assessed from a sample of the cerebrospinal fluid at baseline and at week 48 and change is recorded.
- Immunoglobulin type G index [ Time Frame: 0-48 weeks ]Is assessed from a sample of the cerebrospinal fluid at baseline and at week 48 and change is recorded.
- Cerebrospinal fluid-serum albumin quotient [ Time Frame: 0-48 weeks ]Is assessed from a sample of the cerebrospinal fluid at baseline and at week 48 and change is recorded.
- Chitinase 3 like 1 [ Time Frame: 0-48 weeks ]Is assessed from a sample of the cerebrospinal fluid at baseline and at week 48 and change is recorded.
- matrix metalloproteinase 9 [ Time Frame: 0-48 weeks ]Is assessed from a sample of the cerebrospinal fluid at baseline and at week 48 and change is recorded.
- C-X-C motif chemokine ligand 13 (CXCL13) [ Time Frame: 0-48 weeks ]Is assessed from a sample of the cerebrospinal fluid at baseline and at week 48 and change is recorded.
- Myelin Basic protein [ Time Frame: 0-48 weeks ]Is assessed from a sample of the cerebrospinal fluid at baseline and at week 48 and change is recorded.
- Number of Gadolinium enhancing lesions on MRI [ Time Frame: 0-48 weeks ]Is assessed on MRI performed at baseline and at week 48. Change is recorded.
- Number of new or enlarged T2 lesions on MRI [ Time Frame: 0-48 weeks ]Is assessed on MRI performed at baseline and at week 48. Change is recorded.
- Percentage brain volume change [ Time Frame: 0-48 weeks ]Is assessed on MRI performed at baseline and at week 48. Change is recorded.
- Volume of T2 lesions, cortical grey matter (CGM), putamen, thalamus and normal-appearing white matter (NAWM) on MRI [ Time Frame: 0-48 weeks ]Is assessed
Original Secondary Outcome:
- Expanded Disability Status Scale (EDSS) [ Time Frame: 0-48 weeks ]Is assesed by neurostatus 03/09 by either the primary investigator or another medical doctor to whom the task has been delegated. The evaluation is performed at baseline and at week 48 and change is recorded.
- Timed 25-Foot Walk (T25FW) [ Time Frame: 0-48 weeks ]Is assessed by a trained research nurse, the primary investigator or another medical doctor to whom the task has been delegated. The test is performed at baseline and at week 48 and change is recorded.
- Nine hole peg test (9HPT) [ Time Frame: 0-48 weeks ]Is assessed by a trained research nurse, the primary investigator or another medical doctor to whom the task has been delegated. The test is performed at baseline and at week 48 and change is recorded.
- Symbol digit modalities test (SDMT) [ Time Frame: 0-48 weeks ]Is assessed by a trained research nurse, the primary investigator or another medical doctor to whom the task has been delegated. The test is performed at baseline and at week 48 and change is recorded.
- Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) [ Time Frame: 0-48 weeks ]Is assessed by a trained research nurse, the primary investigator or another medical doctor to whom the task has been delegated. The test is performed at baseline and at week 48 and change is recorded.
- Low contrast visual acuity (LCVA) [ Time Frame: 0-48 weeks ]Is assessed by a trained research nurse, the primary investigator or another medical doctor to whom the task has been delegated. The test is performed at baseline and at week 48 and change is recorded.
- Urinary distress inventory (UDI) [ Time Frame: 0-48 weeks ]Is assessed by questionnaire. The questionnaire is handed out at baseline and at week 48 and change is recorded.
- Fatigue Scale for Motor and Cognitive Functions (FSMC) [ Time Frame: 0-48 weeks ]Is assessed by questionnaire. The questionnaire is handed out at baseline and at week 48 and change is recorded.
- Multiple Sclerosis Impact Scale 29 (MSIS-29) [ Time Frame: 0-48 weeks ]Is assessed by questionnaire. The questionnaire is handed out at baseline and at week 48 and change is recorded.
- Cerebrospinal fluid cell count [ Time Frame: 0-48 weeks ]Is assessed from a sample of the cerebrospinal fluid at baseline and at week 48 and change is recorded.
- Immunoglobuline type G index [ Time Frame: 0-48 weeks ]Is assessed from a sample of the cerebrospinal fluid at baseline and at week 48 and change is recorded.
- Cerebrospinal fluid-serum albumin quotient [ Time Frame: 0-48 weeks ]Is assessed from a sample of the cerebrospinal fluid at baseline and at week 48 and change is recorded.
- Chitinase 3 like 1 [ Time Frame: 0-48 weeks ]Is assessed from a sample of the cerebrospinal fluid at baseline and at week 48 and change is recorded.
- matrix metalloproteinase 9 [ Time Frame: 0-48 weeks ]Is assessed from a sample of the cerebrospinal fluid at baseline and at week 48 and change is recorded.
- CXC chemokine ligand 13 [ Time Frame: 0-48 weeks ]Is assessed from a sample of the cerebrospinal fluid at baseline and at week 48 and change is recorded.
- Myelin Basic protein [ Time Frame: 0-48 weeks ]Is assessed from a sample of the cerebrospinal fluid at baseline and at week 48 and change is recorded.
- Number of Gadolinium enhancing lesions on MRI [ Time Frame: 0-48 weeks ]Is assesed on MRI performed at baseline and at week 48. Change is recorded.
- Number of new or enlarged T2 lesions on MRI [ Time Frame: 0-48 weeks ]Is assesed on MRI performed at baseline and at week 48. Change is recorded.
- Percentage brain volume change [ Time Frame: 0-48 weeks ]Is assesed on MRI performed at baseline and at week 48. Change is recorded.
- Volume of T2 lesions, cortical grey matter (CGM), putamen, thalamus and normal-appearing white matter (NAWM) on MRI [ Time Frame: 0-48 weeks ]Is assesed on MRI performed at b
Information By: Rigshospitalet, Denmark
Dates:
Date Received: November 8, 2016
Date Started: November 2016
Date Completion: December 2019
Last Updated: December 2, 2016
Last Verified: December 2016
- Expanded Disability Status Scale (EDSS) [ Time Frame: 0-48 weeks ]
