Simvastatin as an Add-on Treatment to Interferon-beta-1a for the Treatment of Relapsing-Remitting Multiple Sclerosis (SIMCOMBIN)

• ClinicalTrials.gov Identifier: NCT00492765
• Recruitment Status: Completed
• First Posted: June 27, 2007
• Last Update Posted: October 15, 2010
• Sponsor: Biogen
• Information provided by: Biogen

Study Description

Brief Summary:

This study is to find out if there is any benefit to adding Simvastatin to Interferon-beta-1a in patients with Multiple Sclerosis.

Condition or disease	Intervention/treatment	Phase
Multiple Sclerosis	Drug: Interferon-beta-1a; Drug: Simvastatin; Drug: Placebo	Phase 4

Detailed Description:

This is a multi-centre, double blind, placebo controlled, randomised, parallel group, phase 4 study. Following three months treatment with Interferon beta 1a (Avonex) patients will be randomised for treatment with simvastatin or placebo as an add-on to interferon -beta-1a (AvonexÒ). Patients will start treatment with 40 mg peroral simvastatin daily or identically appearing placebo for one month. Hereafter, patients will escalate dosage to 80 mg daily. The patients will be examined clinically at baseline and at, 3, 4, 6, 9, 12 and 15 months. Patients who attend visit 5 (15 months) before the last patient has attended this visit will be asked to attend additional visits (visits 6+) until the last patient has attended visit 5. Clinical examination will be performed, for applicable patients, at 3 month intervals until the end of the study. This will be a maximum of two years, i.e. no more than eight additional visits. Laboratory assessments will be performed at screening 3, 4, 6, 9, 12 and 15 months after baseline, and for applicable patients additionally at 3 month intervals until end of study. MRI will be performed (T1-weighted and T2-weighted) at randomisation (3 months after baseline) and 12 months hereafter.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 380 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multi-centre, Double Blind, Randomised, Placebo Controlled, Parallel Group Study Investigating Simvastatin as an Add-on Treatment IM Administered Interferon-beta-1a for the Treatment of Relapsing-Remitting Multiple Sclerosis
• Study Start Date: February 2006
• Actual Primary Completion Date: April 2010
• Actual Study Completion Date: April 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1; interferon beta-1a and Simvastatin	Drug: Interferon-beta-1a; dosage and frequency as per label; Other Name: Avonex; Drug: Simvastatin; dosage and frequency as per Biogen Idec protocol
Placebo Comparator: 2; Interferon beta-1a and Placebo	Drug: Interferon-beta-1a; dosage and frequency as per label; Other Name: Avonex; Drug: Placebo; dosage and frequency the same as simvastatin as per Biogen Idec Protocol

Outcome Measures

Primary Outcome Measures :

1. The time to first documented relapse [ Time Frame: months 4, 6, 9, 12, and every 3 months from months 18-39 ]

Secondary Outcome Measures :

1. 3Annual rate of documented relapses after randomisation [ Time Frame: months 4, 6, 9, 12, and every 3 months from months 18-39 ]
2. Number of new and/or enlarging lesions on T2-weighted MRI based on MRI done 12 months following randomisation compared with MRI done at time of randomisation [ Time Frame: month 15 ]
3. Proportion of patients without disease activity after randomisation (i.e. no relapses, no increase in EDSS score and no increase in enlarging or new T2 lesions). [ Time Frame: months 4, 6, 9, 12, and every 6 months from months 18-39 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Is between the age of 18 and 55 years (both included)
• Relapsing-remitting MS according to Poser criteria (CDMS or LSDMS) 22 or definite MS according to McDonald criteria 23
• Disability equivalent to an EDSS of 5.5 or less 21
• Clinical activity defined as at least one reported or documented relapse within the last year
• Patient must be prepared to and considered able to follow the protocol during the whole study period and to attend the planned visits, even if the treatment has to be withdrawn

Exclusion Criteria:

• Any condition that might give rise to similar symptoms as MS
• Immunomodulatory or immunosuppressive treatment for MS prior to inclusion into the study (prior pulse steroid treatment for relapses is allowed)
• Treatment with glucocorticoids or ACTH later than one month prior to inclusion into the study, i.e. at the screening visit
• Onset of a relapse within one month prior to inclusion into the study, i.e. at the screening visit
• History of major depression
• Alcohol or drug dependency
• Cardiac insufficiency, cardiomyopathy, significant cardiac dysrhythmia, unstable or advanced ischemic heart disease (NYHA III or IV)
• Significant hypertension (BP > 180/110 mmHg)
• Renal insufficiency defined as serum creatinine > 1.5 times the upper normal reference limit
• Total plasma cholesterol < 3.5 mmol/L
• Any medical illness requiring treatment with systemic corticosteroids
• Any systemic disease that can influence the patient's safety and compliance, or the evaluation of the disability
• Women who are pregnant, breast-feeding or have the possibility for pregnancy during the study. To avoid pregnancy, women have to be postmenopausal, surgically sterile, sexually inactive or practice reliable contraception

Contacts and Locations

Locations

Denmark

Coordinating Research Site

Copenhagen, Denmark

Sponsors and Collaborators

Biogen

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Sorensen PS, Lycke J, Erälinna JP, Edland A, Wu X, Frederiksen JL, Oturai A, Malmeström C, Stenager E, Sellebjerg F, Sondergaard HB; SIMCOMBIN study investigators. Simvastatin as add-on therapy to interferon β-1a for relapsing-remitting multiple sclerosis (SIMCOMBIN study): a placebo-controlled randomised phase 4 trial. Lancet Neurol. 2011 Aug;10(8):691-701. doi: 10.1016/S1474-4422(11)70144-2.

• Responsible Party: Biogen Idec MD, Biogen Idec
• ClinicalTrials.gov Identifier: NCT00492765
• Other Study ID Numbers: SIMCOMBIN
• First Posted: June 27, 2007
• Last Update Posted: October 15, 2010
• Last Verified: October 2010

Keywords provided by Biogen:

Combination therapy; Simvastatin; Multiple Sclerosis; Interferon-beta-1a

Additional relevant MeSH terms:

Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis; Pathologic Processes; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Interferons; Interferon-beta; Interferon beta-1a; Simvastatin; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors; Immunologic Factors; Physiological Effects of Drugs; Adjuvants, Immunologic