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

Primary Purpose

Multiple Sclerosis

Status
Completed
Phase
Phase 4
Locations
Denmark
Study Type
Interventional
Intervention
Interferon-beta-1a
Simvastatin
Placebo
Sponsored by
Biogen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Sclerosis focused on measuring Combination therapy, Simvastatin, Multiple Sclerosis, Interferon-beta-1a

Eligibility Criteria

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

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to follow the protocol during the whole study period and to attend the planned visits, even if the treatment has to be withdrawn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

Sites / Locations

  • Coordinating Research Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

1

2

Arm Description

interferon beta-1a and Simvastatin

Interferon beta-1a and Placebo

Outcomes

Primary Outcome Measures

The time to first documented relapse

Secondary Outcome Measures

3Annual rate of documented relapses after randomisation
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
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).

Full Information

First Posted
June 25, 2007
Last Updated
October 14, 2010
Sponsor
Biogen
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1. Study Identification

Unique Protocol Identification Number
NCT00492765
Brief Title
Simvastatin as an Add-on Treatment to Interferon-beta-1a for the Treatment of Relapsing-Remitting Multiple Sclerosis
Acronym
SIMCOMBIN
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 Type
Interventional

2. Study Status

Record Verification Date
October 2010
Overall Recruitment Status
Completed
Study Start Date
February 2006 (undefined)
Primary Completion Date
April 2010 (Actual)
Study Completion Date
April 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Biogen

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
Keywords
Combination therapy, Simvastatin, Multiple Sclerosis, Interferon-beta-1a

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
380 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
interferon beta-1a and Simvastatin
Arm Title
2
Arm Type
Placebo Comparator
Arm Description
Interferon beta-1a and Placebo
Intervention Type
Drug
Intervention Name(s)
Interferon-beta-1a
Other Intervention Name(s)
Avonex
Intervention Description
dosage and frequency as per label
Intervention Type
Drug
Intervention Name(s)
Simvastatin
Intervention Description
dosage and frequency as per Biogen Idec protocol
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
dosage and frequency the same as simvastatin as per Biogen Idec Protocol
Primary Outcome Measure Information:
Title
The time to first documented relapse
Time Frame
months 4, 6, 9, 12, and every 3 months from months 18-39
Secondary Outcome Measure Information:
Title
3Annual rate of documented relapses after randomisation
Time Frame
months 4, 6, 9, 12, and every 3 months from months 18-39
Title
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
Title
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

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: 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
Facility Information:
Facility Name
Coordinating Research Site
City
Copenhagen
Country
Denmark

12. IPD Sharing Statement

Citations:
PubMed Identifier
21742556
Citation
Sorensen PS, Lycke J, Eralinna JP, Edland A, Wu X, Frederiksen JL, Oturai A, Malmestrom C, Stenager E, Sellebjerg F, Sondergaard HB; SIMCOMBIN study investigators. Simvastatin as add-on therapy to interferon beta-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.
Results Reference
derived

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

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