Clinical trial NCT00360906: Omega-3 Fatty Acid Treatment in Multiple Sclerosis
Official title: Omega-3 Fatty Acid Treatment in Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Relapsing-Remitting Multiple Sclerosis
Keywords: RRMS
Omega-3
Treatment
Lead sponsor: Haukeland University Hospital
Sponsor class: OTHER
Collaborators: name: The Multiple Sclerosis National Competence Centre
name: The Norwegian Multiple sclerosis Society
name: Pronova BioPharma
name: Serono Nordic
name: Amersham Health
First posted: 2006-08-07
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: MRI disease activity measured by the number of new T1-enhancing lesions during the six months of treatment.
measure: MRI disease activity measured by the number of new T1-hypo-intensive lesions (black holes) after 24 months of treatment.
Secondary outcomes:
measure: 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.
measure: Brain atrophy measured by total MRI brain volume at month 6 and month 24
measure: The number of relapses during the first six months and the whole study period of 24 months.
measure: 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.
measure: Changes in the Multiple Sclerosis Functional Composite (MSFC) score during the first six months and the whole study period of 24 months.
measure: 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.
measure: Changes in serum concentrations of mono-unsaturated fatty acids, saturated fatty acids, omega-3- and omega-6 fatty acids during the study.
measure: Changes in immune responses during the first six months and the whole study period of 24 months.
measure: The occurrence of adverse events during the first six months and the whole study period of 24 months.
measure: The occurrence of adverse events during the first three months of interferon-beta 1a (Rebif®) treatment.
measure: The occurrence of neutralising antibodies against interferon-beta 1a (Rebif®) during the study.
Other outcomes:
Locations:
city: Bergen
country: Norway
facility: Department of Neurology, Haukeland University Hospital
Study officials:
affiliation: Dep. of Neurology, Haukeland University Hospital
name: Kjell-Morten Myhr, MD, PhD
role: STUDY_CHAIR
affiliation: Dep. of Neurology, Akershus University Hospital
name: Antonie G. Beiske, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dep. of Neurology, Trondheim University Hospital
name: Harald Hovdal, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dep. of Neurology, Molde Hospital
name: Rune Midgard, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dep. of Neurology, Buskerud Hospital
name: Ingrid K. Bjørnå, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dep. of Neurology Nordland Hospital
name: Olaf A. Henriksen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dep. of Neurology Haugesund Hospital
name: Jan Schepel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dep. of Neurology Arendal Hospital
name: Randi Eikeland, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dep. of Neurology Fredrikstad Hospital
name: Terje Kristensen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dep. of Neurology Rikshospitalet University Hospital
name: Halfdan Kierulf, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dep. of Neurology, Telemark Hospital
name: Frøydis Dalane, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dep. of Neurology, Stavanger University Hospital
name: Alla Bru, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dep. of Neurology, Lillehammer Hospital
name: Grethe Kleveland, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.