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

This study has been completed.
Sponsor:
Information provided by:
Biogen Idec
ClinicalTrials.gov Identifier:
NCT00492765
First received: June 25, 2007
Last updated: October 14, 2010
Last verified: October 2010
  Purpose

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


Condition Intervention Phase
Multiple Sclerosis
Drug: Interferon-beta-1a
Drug: Simvastatin
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Biogen Idec:

Primary Outcome Measures:
  • The time to first documented relapse [ Time Frame: months 4, 6, 9, 12, and every 3 months from months 18-39 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 3Annual rate of documented relapses after randomisation [ Time Frame: months 4, 6, 9, 12, and every 3 months from months 18-39 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 380
Study Start Date: February 2006
Study Completion Date: April 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00492765

Locations
Denmark
Coordinating Research Site
Copenhagen, Denmark
Sponsors and Collaborators
Biogen Idec
  More Information

No publications provided by Biogen Idec

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Biogen Idec MD, Biogen Idec
ClinicalTrials.gov Identifier: NCT00492765     History of Changes
Other Study ID Numbers: SIMCOMBIN
Study First Received: June 25, 2007
Last Updated: October 14, 2010
Health Authority: Denmark: Danish Medicines Agency
Finland: Finnish Medicines Agency
Norway: Norwegian Medicines Agency
Sweden: Medical Products Agency

Keywords provided by Biogen Idec:
Combination therapy
Simvastatin
Multiple Sclerosis
Interferon-beta-1a

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

ClinicalTrials.gov processed this record on October 21, 2014