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Omega-3 Fatty Acid Treatment in Multiple Sclerosis

Primary Purpose

Relapsing-Remitting Multiple Sclerosis

Status
Completed
Phase
Phase 2
Locations
Norway
Study Type
Interventional
Intervention
Triomar™ (omega-3 fatty acids)
Sponsored by
Haukeland University Hospital
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsing-Remitting Multiple Sclerosis focused on measuring RRMS, Omega-3, Treatment

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: A patient may be included if he/she; Is aged between 18 and 55 years (both included). Has multiple sclerosis according to the McDonald criteria (McDonald 2001) Has a stable disease during the last month period prior to inclusion, and a disability equivalent to EDSS of 5.5 or less (Kurtzke 1983). Has shown disease activity defined as at least one relapse or at least one new MRI lesion (T1 enhancing or T2 lesion - ref. McDonald criteria) during the year prior to inclusion. Is prepared to and considered able to follow the protocol and to attend the planned visits during the whole study period. Is using adequate contraceptive methods and has negative pregnancy test results (female of childbearing potential must). Has given written informed consent. Exclusion Criteria: A patient has to be excluded if he/she; Has received continuous for more than one-week treatment with unsaturated fatty acids (omega-3) within 3 months prior to inclusion in the study. Has an active RRMS disease that would strongly be recommended for standard immunomodulatory treatment by the treating neurologist. Has received treatment with interferon-beta or glatiramer acetate within 6 months prior to inclusion in the study. Has received treatment with lymphoid irradiation, mitoxantrone, cyclophosphamide or long-term glucocorticoids. Has received treatment with azathioprine, cyclosporine or other immunosuppressive agents within the year prior to inclusion in the study. Has received treatment with glucocorticoids or ACTH within two month prior to inclusion in the study. Has experienced a relapse within one month prior to the inclusion in the study. Has converted to secondary progressive MS. Has suffered from major depression or any other psychiatric disorder that would preclude safe participation in the protocol. Has diabetes mellitus. Has alcohol or drug abuse. Has cardiac insufficiency, cardiomyopathy, significant cardiac dysrhythmia, unstable or advanced ischemic heart disease (NYHA III or IV), or malignant hypertension. Has renal insufficiency. Has ASAT or ALAT > 2,5 x normal upper limit. Has leukopenia < 2500 leukocytes per µl or thrombocytopenia <100 000 thrombocytes per µl. Has any systemic disease, which can influence his/her safety and compliance, or the evaluation of the disability. Has thromboembolic disease that needs anticoagulative treatment. Have formerly shown severe reactions against study drug, interferon-beta or gadolinium (MRI contrast). Is breastfeeding or is pregnant.

Sites / Locations

  • Department of Neurology, Haukeland University Hospital

Outcomes

Primary Outcome Measures

MRI disease activity measured by the number of new T1-enhancing lesions during the six months of treatment.
MRI disease activity measured by the number of new T1-hypo-intensive lesions (black holes) after 24 months of treatment.

Secondary Outcome Measures

MRI disease activity measured by the number of new T1-enhancing lesions during the first 9 months and the whole study period of 24 months.
Brain atrophy measured by total MRI brain volume at month 6 and month 24
The number of relapses during the first six months and the whole study period of 24 months.
The increase in disability as measured by Expanded Disability Status Scale (EDSS) during the first six months and the whole study period of 24 months.
Changes in the Multiple Sclerosis Functional Composite (MSFC) score during the first six months and the whole study period of 24 months.
MRI disease activity as measured by the number of new or enlarging T2 lesions and enhancing T1 lesions during the first six months and the whole study period of 24 months.
Changes in serum concentrations of mono-unsaturated fatty acids, saturated fatty acids, omega-3- and omega-6 fatty acids during the study.
Changes in immune responses during the first six months and the whole study period of 24 months.
The occurrence of adverse events during the first six months and the whole study period of 24 months.
The occurrence of adverse events during the first three months of interferon-beta 1a (Rebif®) treatment.
The occurrence of neutralising antibodies against interferon-beta 1a (Rebif®) during the study.

Full Information

First Posted
August 4, 2006
Last Updated
August 4, 2006
Sponsor
Haukeland University Hospital
Collaborators
The Multiple Sclerosis National Competence Centre, The Norwegian Multiple sclerosis Society, Pronova BioPharma, Serono Nordic, Amersham Health
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1. Study Identification

Unique Protocol Identification Number
NCT00360906
Brief Title
Omega-3 Fatty Acid Treatment in Multiple Sclerosis
Official Title
Omega-3 Fatty Acid Treatment in Multiple Sclerosis
Study Type
Interventional

2. Study Status

Record Verification Date
August 2006
Overall Recruitment Status
Completed
Study Start Date
December 2004 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
July 2008 (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Haukeland University Hospital
Collaborators
The Multiple Sclerosis National Competence Centre, The Norwegian Multiple sclerosis Society, Pronova BioPharma, Serono Nordic, Amersham Health

4. Oversight

5. Study Description

Brief Summary
Based on previous clinical studies indicating beneficial treatment effects of omega-3 fatty acids in multiple sclerosis, and the increasing evidence of anti-inflammatory effects of omega-3 fatty acids, this study aims to evaluate treatment effects of concentrated omega-3 fatty acids (Triomar™) in MS, both as monotherapy and in combination with standard immunomodulatory therapy defined as interferon-beta 1a (Rebif™).
Detailed Description
Patients with relapsing-remitting multiple sclerosis with evidence of disease activity defined as at least one relapse or at least one new MRI lesion during the year prior to inclusion will be included in the study. Eligible patients will be randomised for daily treatment with either oral omega-3 fatty acid (Triomar™) or placebo. After six months all patients will in addition receive interferon-beta 1a (Rebif™) 44 mcg subcutaneous three times per week for another 18 months. The patients will undergo monthly contrast enhanced MRI for the first nine months and thereafter at months 12 and 24. They will also be examined by clinical and laboratory tests at six months intervals in addition to month 9 (3 months after start of IFNB treatment). Fatigue and QoL registration will be performed at baseline and at months 6, 12 and 24. Tests for circulating neutralising antibodies against interferon-beta will be performed during the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsing-Remitting Multiple Sclerosis
Keywords
RRMS, Omega-3, Treatment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
100 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Triomar™ (omega-3 fatty acids)
Primary Outcome Measure Information:
Title
MRI disease activity measured by the number of new T1-enhancing lesions during the six months of treatment.
Title
MRI disease activity measured by the number of new T1-hypo-intensive lesions (black holes) after 24 months of treatment.
Secondary Outcome Measure Information:
Title
MRI disease activity measured by the number of new T1-enhancing lesions during the first 9 months and the whole study period of 24 months.
Title
Brain atrophy measured by total MRI brain volume at month 6 and month 24
Title
The number of relapses during the first six months and the whole study period of 24 months.
Title
The increase in disability as measured by Expanded Disability Status Scale (EDSS) during the first six months and the whole study period of 24 months.
Title
Changes in the Multiple Sclerosis Functional Composite (MSFC) score during the first six months and the whole study period of 24 months.
Title
MRI disease activity as measured by the number of new or enlarging T2 lesions and enhancing T1 lesions during the first six months and the whole study period of 24 months.
Title
Changes in serum concentrations of mono-unsaturated fatty acids, saturated fatty acids, omega-3- and omega-6 fatty acids during the study.
Title
Changes in immune responses during the first six months and the whole study period of 24 months.
Title
The occurrence of adverse events during the first six months and the whole study period of 24 months.
Title
The occurrence of adverse events during the first three months of interferon-beta 1a (Rebif®) treatment.
Title
The occurrence of neutralising antibodies against interferon-beta 1a (Rebif®) during the study.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: A patient may be included if he/she; Is aged between 18 and 55 years (both included). Has multiple sclerosis according to the McDonald criteria (McDonald 2001) Has a stable disease during the last month period prior to inclusion, and a disability equivalent to EDSS of 5.5 or less (Kurtzke 1983). Has shown disease activity defined as at least one relapse or at least one new MRI lesion (T1 enhancing or T2 lesion - ref. McDonald criteria) during the year prior to inclusion. Is prepared to and considered able to follow the protocol and to attend the planned visits during the whole study period. Is using adequate contraceptive methods and has negative pregnancy test results (female of childbearing potential must). Has given written informed consent. Exclusion Criteria: A patient has to be excluded if he/she; Has received continuous for more than one-week treatment with unsaturated fatty acids (omega-3) within 3 months prior to inclusion in the study. Has an active RRMS disease that would strongly be recommended for standard immunomodulatory treatment by the treating neurologist. Has received treatment with interferon-beta or glatiramer acetate within 6 months prior to inclusion in the study. Has received treatment with lymphoid irradiation, mitoxantrone, cyclophosphamide or long-term glucocorticoids. Has received treatment with azathioprine, cyclosporine or other immunosuppressive agents within the year prior to inclusion in the study. Has received treatment with glucocorticoids or ACTH within two month prior to inclusion in the study. Has experienced a relapse within one month prior to the inclusion in the study. Has converted to secondary progressive MS. Has suffered from major depression or any other psychiatric disorder that would preclude safe participation in the protocol. Has diabetes mellitus. Has alcohol or drug abuse. Has cardiac insufficiency, cardiomyopathy, significant cardiac dysrhythmia, unstable or advanced ischemic heart disease (NYHA III or IV), or malignant hypertension. Has renal insufficiency. Has ASAT or ALAT > 2,5 x normal upper limit. Has leukopenia < 2500 leukocytes per µl or thrombocytopenia <100 000 thrombocytes per µl. Has any systemic disease, which can influence his/her safety and compliance, or the evaluation of the disability. Has thromboembolic disease that needs anticoagulative treatment. Have formerly shown severe reactions against study drug, interferon-beta or gadolinium (MRI contrast). Is breastfeeding or is pregnant.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kjell-Morten Myhr, MD, PhD
Organizational Affiliation
Dep. of Neurology, Haukeland University Hospital
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Antonie G. Beiske, MD
Organizational Affiliation
Dep. of Neurology, Akershus University Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Harald Hovdal, MD
Organizational Affiliation
Dep. of Neurology, Trondheim University Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Rune Midgard, MD, PhD
Organizational Affiliation
Dep. of Neurology, Molde Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ingrid K. Bjørnå, MD
Organizational Affiliation
Dep. of Neurology, Buskerud Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Olaf A. Henriksen, MD
Organizational Affiliation
Dep. of Neurology Nordland Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jan Schepel, MD
Organizational Affiliation
Dep. of Neurology Haugesund Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Randi Eikeland, MD
Organizational Affiliation
Dep. of Neurology Arendal Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Terje Kristensen, MD
Organizational Affiliation
Dep. of Neurology Fredrikstad Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Halfdan Kierulf, MD
Organizational Affiliation
Dep. of Neurology Rikshospitalet University Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Frøydis Dalane, MD
Organizational Affiliation
Dep. of Neurology, Telemark Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Alla Bru, MD
Organizational Affiliation
Dep. of Neurology, Stavanger University Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Grethe Kleveland, MD
Organizational Affiliation
Dep. of Neurology, Lillehammer Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Neurology, Haukeland University Hospital
City
Bergen
ZIP/Postal Code
N-5021
Country
Norway

12. IPD Sharing Statement

Citations:
PubMed Identifier
10987373
Citation
Nordvik I, Myhr KM, Nyland H, Bjerve KS. Effect of dietary advice and n-3 supplementation in newly diagnosed MS patients. Acta Neurol Scand. 2000 Sep;102(3):143-9. doi: 10.1034/j.1600-0404.2000.102003143.x.
Results Reference
background
PubMed Identifier
34978580
Citation
Lie IA, Kerklingh E, Wesnes K, van Nederpelt DR, Brouwer I, Torkildsen O, Myhr KM, Barkhof F, Bo L, Vrenken H. The effect of gadolinium-based contrast-agents on automated brain atrophy measurements by FreeSurfer in patients with multiple sclerosis. Eur Radiol. 2022 May;32(5):3576-3587. doi: 10.1007/s00330-021-08405-8. Epub 2022 Jan 3.
Results Reference
derived
PubMed Identifier
29209636
Citation
Varhaug KN, Barro C, Bjornevik K, Myhr KM, Torkildsen O, Wergeland S, Bindoff LA, Kuhle J, Vedeler C. Neurofilament light chain predicts disease activity in relapsing-remitting MS. Neurol Neuroimmunol Neuroinflamm. 2017 Nov 28;5(1):e422. doi: 10.1212/NXI.0000000000000422. eCollection 2018 Jan.
Results Reference
derived
PubMed Identifier
22507886
Citation
Torkildsen O, Wergeland S, Bakke S, Beiske AG, Bjerve KS, Hovdal H, Midgard R, Lilleas F, Pedersen T, Bjornara B, Dalene F, Kleveland G, Schepel J, Olsen IC, Myhr KM. omega-3 fatty acid treatment in multiple sclerosis (OFAMS Study): a randomized, double-blind, placebo-controlled trial. Arch Neurol. 2012 Aug;69(8):1044-51. doi: 10.1001/archneurol.2012.283.
Results Reference
derived

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Omega-3 Fatty Acid Treatment in Multiple Sclerosis

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