Multiple Sclerosis-Simvastatin Trial 2

Summary

Multiple Sclerosis (MS) is a progressive neurological disorder of the brain and spinal cord. It affects approximately 120,000 people in the United Kingdom and 2.5 million people globally. Most people with MS experience two stages of the disease:

Early MS - Relapsing-Remitting MS (RRMS), which is partially reversible, and Late MS - Secondary Progressive MS (SPMS), which affects the majority of patients, usually after 10 to 15 years after diagnosis.

SPMS results from progressive neuronal degeneration that causes accumulating and irreversible disability affecting walking, balance, manual function, vision, cognition, pain control, bladder and bowel function. The pathological process driving the accrual of disability in SPMS is not known at present.

Immunomodulatory anti-inflammatory disease modifying therapies (DMTs) are increasingly effective in reducing relapse frequency in RRMS, however, they have been unsuccessful in slowing disease progression in SPMS. This is the overwhelming conclusion from an analysis of 18 phase 3 trials (n=8500), of which 70% of the population had SPMS, all performed in the last 25 years.

In an earlier study (Multiple Sclerosis-Simvastatin 1; MS-STAT1), 140 people with SPMS were randomly assigned to receive either placebo or simvastatin for a period of two years. The investigators found that the rate of brain atrophy (loss of neurons - 'brain shrinkage'), as measured by magnetic resonance imaging (MRI), was reduced in patients receiving simvastatin compared to those taking placebo.

Several other long term studies have also reported that there might be a relationship between the rate of brain atrophy and the degree of impairment. The study is designed to test the effectiveness of repurposed simvastatin (80mg) in a phase 3 double blind, randomised, placebo controlled trial (1:1) in patients with secondary progressive MS (SPMS), to determine if the rate of disability progression can be slowed over a 3 to 4.5 year period.

The results generated from this trial may help to improve the treatment options of people with MS. In addition, taking part in this trial will mean regular review by an experienced neurologist regardless of the drug that patients are randomly allocated to receive.

Conditions

• Secondary Progressive Multiple Sclerosis (SPMS)

Interventions

DRUG

Simvastatin

* One (1 = 40mg) simvastatin tablet once daily at night for 1 month * Two (2 = 80mg) simvastatin tablets once daily at night, for the next 35 to 53 months

DRUG

Placebo

* One (1) placebo tablet once daily at night for 1 month * Two (2) placebo tablets once daily at night, for the next 35 to 53 months

Sponsors & Collaborators

• University of Edinburgh

  collaborator OTHER

• Queen Mary University of London

  collaborator OTHER

• London School of Hygiene and Tropical Medicine

  collaborator OTHER

• University of Leeds

  collaborator OTHER

• The Leeds Teaching Hospitals NHS Trust

  collaborator OTHER

• Imperial College Healthcare NHS Trust

  collaborator OTHER

• University College, London

  lead OTHER

Principal Investigators

• Jeremy Chataway · University College, London

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

25 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-03-28

Primary Completion

2024-07-26

Completion

2024-08-25

Countries

• United Kingdom

Study Locations