Simvastatin in Secondary Progressive Multiple Sclerosis

• Register: ClinicalTrials.gov
• Last refreshed on: 22 January 2024
• Main ID: NCT03896217
• Date of registration: 26/10/2018
• Prospective Registration: Yes
• Primary sponsor: University College, London
• Public title: Simvastatin in Secondary Progressive Multiple Sclerosis MS-OPT
• Scientific title: A Double-blind, Randomised, Placebo-controlled Single-site Study of High Dose Simvastatin Treatment for Secondary Progressive Multiple Sclerosis: Impact on Vascular Perfusion and Oxidative Damage
• Date of first enrolment: May 16, 2019
• Target sample size: 40
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT03896217
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Single (Participant).
• Phase: Phase 2

Countries of recruitment

United Kingdom

Contacts

• Name: Richard Nicholas, MD
• Affiliation: UCL

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Patients must have a confirmed diagnosis of multiple sclerosis according to revised Mc
Donald criteria and have entered the secondary progressive stage. (Polman et al.,
2011, Lublin, 2014) Steady progression rather than relapse must be the major cause of
increasing disability in the preceding 2 years. Progression can be evident from either
an increase of at least one point on the EDSS or clinical documentation of increasing
disability.

2. EDSS 4.0 - 6.5 (inclusive).

3. Male and Females aged 18 to 65

4. Females of childbearing potential and males with partners who are of childbearing age
must be willing to use an effective method of contraception (Double barrier method of
birth control or True abstinence) from the time consent is signed until 6 weeks after
treatment discontinuation and inform the trial team if pregnancy occurs. For the
purpose of clarity, True abstinence is when this is in line with the preferred and
usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation,
symptothermal, post-ovulation methods), declaration of abstinence, withdrawal,
spermicides only or lactational amenorrhoea method for the duration of a trial, are
not acceptable methods of contraception.

5. Females of childbearing potential have a negative pregnancy test within 7 days prior
to being registered/randomised. Participants are considered not of child bearing
potential if they are surgically sterile (i.e. they have undergone a hysterectomy,
bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal.

6. Willing and able to comply with the trial protocol (e.g. can tolerate MRI and fulfils
the requirements for MRI, e.g. not fitted with pacemakers or permanent hearing aids)
ability to understand and complete questionnaires

7. Willing and able to provide written informed consent

8. Willing to ingest gelatine (placebo will contain this). Participants must therefore be
informed sensitive to personal beliefs e.g. faith, diet.

Exclusion criteria

1. Unable to give informed consent.

2. Primary progressive MS.

3. Those that have experienced a relapse or have been treated with steroids (both i.v.
and oral) for multiple sclerosis relapse within 3 months of the screening visit. These
patients may undergo a further screening visit once the 3 month window has expired and
may be included if no steroid treatment has been administered in the intervening
period. Patients on steroids for another medical condition may enter as long as the
steroid prescription is not for multiple sclerosis (relapse/ progression).

4. Patient is already taking or is anticipated to be taking a statin or lomitapide for
cholesterol control.

5. Any medications that unfavourably interact with statins as per Spc recommendations
e.g.: fibrates, nicotinic acid, cyclosporin, azole anti-fungal preparations,
macrolideantibiotics, protease inhibitors, nefazodone, verapamil, amiodarone, large
amounts of grapefruit juice or alcohol abuse within 6 months.

6. The use of immunosuppressants (e.g. azathioprine, methotrexate, cyclosporin) or
disease modifying treatments (avonex, rebif, betaferon, glatiramer, dimethyl fumerate,
fingolimod) within the previous 6 months.

7. The use of mitoxantrone if treated within the last 12 months.

8. Patient has received treatment with alemtuzumab.

9. Use of other experimental disease modifying treatment (including research in an
investigational medicinal product) within 6 months of baseline visit

10. Active Hepatic disease or known severe renal failure (creatinine clearance <30ml/min)

11. Screening levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST)
or creatine kinase (CK) are three times the upper limit of normal patients.

12. If the patient reports any ophthalmic conditions such as glaucoma, ocular trauma or
degenerative eye disease

13. Patient unable to tolerate or unsuitable to have baseline MRI scan (e.g. metal
implants, heart pacemaker) or MRI scan not of adequate quality for analysis (e.g. too
much movement artefact).

14. Females who are pregnant, planning pregnancy or breastfeeding.

15. Allergies to IMP active substance or to any excipients of IMP and placebo or other
conditions that contraindicate use of galactose (eg. Hereditary galactose intolerance,
Lactase deficiency, glucose-galactose malabsorption).



Age minimum: 18 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Secondary Progressive Multiple Sclerosis

Intervention(s)

Drug: Simvastatin

Primary Outcome(s)

Effect on cerebral blood flow [Time Frame: Over 20 weeks]

Secondary Outcome(s)

Clinical Outcomes: MSFC: 25 foot timed walk [Time Frame: At Day 0 (Baseline), Week 16 and Week 20]

MRI: Neurite density and orientation dispersion imaging [Time Frame: At Day 0 (Baseline), Week 16 and Week 20]

Clinical Outcomes: MSFC: 9 hole peg test [Time Frame: At Day 0 (Baseline), Week 16 and Week 20]

Health Economic outcomes: EQ5D5L [Time Frame: At Day 0 (Baseline), Week 16 and Week 20]

Retinal Vessel Density [Time Frame: At Day 0 (Baseline), Week 16 and Week 20]

Retinal Vessel Oxygen Saturation [Time Frame: At Day 0 (Baseline), Week 16 and Week 20]

MRI: ASL measurements of blood flow [Time Frame: At Day 0 (Baseline), Week 16 and Week 20]

Exploratory outcomes: immune parameters, and biomarkers. [Time Frame: At Day 0 (Baseline), Week 4, Week 16 and Week 20]

Frontal executive functioning: FAB [Time Frame: At Day 0 and Week 20]

Inner retinal thickness [Time Frame: At Day 0 (Baseline), Week 16 and Week 20]

MRI: brain atrophy [Time Frame: At Day 0 (Baseline), Week 16 and Week 20]

MRI: glutamate levels [Time Frame: At Day 0 (Baseline), Week 16 and Week 20]

AOSLO measurements of blood flow [Time Frame: At Day 0 (Baseline), Week 16 and Week 20]

Clinical Outcomes: MSWSv2 questionnaires. [Time Frame: At Day 0 (Baseline), Week 16 and Week 20]

SDMT [Time Frame: At Day 0 (Baseline), Week 16 and Week 20]

Clinical Outcome: EDSS [Time Frame: At Day 0 (Baseline), Week 16 and Week 20]

Clinical Outcomes: MSIS-29v2 questionnaires. [Time Frame: At Day 0 (Baseline), Week 16 and Week 20]

MRI: Number of new or enlarging T2 lesions [Time Frame: At Day 0 (Baseline), Week 16 and Week 20]

Secondary ID(s)

16/0730 & 2017-003008-30

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Multiple Sclerosis Society