Clinical trial NCT01514370: Dietary Supplement of Curcumin in Subjects With Active Relapsing Multiple Sclerosis Treated With Subcutaneous Interferon Beta 1a
Official title: ProspeCtive Study to Evaluate Efficacy, Safety and tOlerability of Dietary supplemeNT of Curcumin (BCM95) in Subjects With Active Relapsing MultIple Sclerosis Treated With subcutaNeous Interferon Beta 1a 44 mcg Three Times a Week (TIW)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Sclerosis
Keywords: Multiple Sclerosis
Relapsing
Interferon beta 1a
Curcumin
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
Collaborators: name: Merck Serono S.P.A., Italy
First posted: 2012-01-23
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a prospective, monocentric, double blind, placebo controlled, two arm study.

Curcumin is derived from the rhizomes of the plant Curcuma longa (common name, turmeric) belonging to the Zingiberaceae family found in South Asian countries, especially India which is the largest producer. BCM95 (bioCurcumin) is a combination of a Curcumin extract and oil to enhance the bio-absorbability in humans. BCM95 may enhance and prolong the antioxidant and anti-inflammatory effects of the standard therapy maintaining a good safety profile.

Detailed description: The subjects must experience at least one Gadolinium (GD) enhancing Magnetic Resonance Imaging (MRI) lesion at the baseline visit or one Multiple Sclerosis (MS) relapse in the last 6 months before the screening visit.

Randomization, in a 1:1 ratio, will be done with two arms:

40 subjects with Interferon (IFN) beta 1 a 44 mcg TIW + Curcumin (BCM 95) and 40 subjects with IFN beta-1a 44 mcg TIW + placebo.

The study will last 42 months: 18 months of enrolment and 24 months of treatment period.

The study consists of 6 visits per subject: screening visit (Visit 0), baseline (Visit 1), a visit 3 months after baseline (Visit 2), 6 months after baseline (Visit 3), 12 months after baseline (Visit 4) and 24 months after baseline (Visit 5).

Eligibility criteria: Inclusion Criteria:

* Subjects with early diagnosis (no more than 3 years) of Relapsing Multiple Sclerosis according to the revised McDonald Criteria (2010)
* Subjects currently in treatment with IFN beta-1a 44 mcg TIW, having received this treatment a minimum of 6 months and for not longer than 12 months before enrollment.
* Subjects must experience at least one Gd-enhancing MRI lesion at baseline visit or one MS relapse in the last 6 months before screening visit.
* Males and females between 18 - 60 years of age
* Subjects with Expanded Disability Status Scale (EDSS) between 0-5.5
* No use of oral or systemic corticosteroids or corticotropin (ACTH) within 30 days prior to Screening visit. No use of any Disease Modifying Drug (DMD) (other than IFN beta-1a 44 mcg) 12 months prior to Screening visit
* Be willing and able to comply with the protocol
* Signed informed consent

Exclusion Criteria:

* Pregnancy and breast-feeding
* History of alcohol or drug abuse
* Serious psychiatric disorders
* History or presence of serious or acute gastrointestinal disease such as gastric or duodenal ulcer, ulcerative colitis and inflammatory bowel or Crohn's disease
* Subjects suffering by obstruction of the biliary tract
* Any major medical condition that in the opinion of the Investigator could create a risk to the subject or could affect adherence with the trial protocol.
* Subjects with inadequate haematological function (defined by leukocyte ≤ 2,0 x 10\^9 ; platelets ≤ 100 x 10\^9; haemoglobin ≤ 12 g/dl for female and ≤ 13 g/dl for male), liver function (defined by AST, ALT, alkaline phosphatase \> 2.0 times upper limit of normal), thyroid function (In particular subjects with clinically overt hyperthyroidism or clinically overt hypothyroidism and in any case according to physician's discretion).
* Known hypersensitivity to gadolinium
* Any other condition that would prevent the subject from undergoing an MRI scan (impairment of Kidney function, metal prosthesis etc.)
* Immunosuppressive therapy 12 months before screening visit
* Use of some recognized drugs involved as enzyme substrates, inducers or inhibitors in P450 system
* Use of antiplatelet agents or antihyperlipidemics
* Any contra-indication according to IFN beta 1a 44 mcg Summary of Product Characteristics (SmPC)

Primary outcomes:
measure: Number of Subjects With Active (New or Enlarging) T2 Lesions Assessed by Magnetic Resonance Imaging (MRI) at Month 12
timeFrame: Month 12
Secondary outcomes:
measure: Percentage of Relapse-Free Subjects at Month 12 and Month 24
timeFrame: Month 12 and 24
measure: Annualized Relapse Rate at Month 12 and 24
timeFrame: Month 12 and 24
measure: Total Number of Reported Relapses at Month 3, 6, 12 and 24
timeFrame: Month 3, 6, 12 and 24
measure: Percentage of Subjects Treated With Glucocorticoids Due to Relapses During 24 Months
timeFrame: Baseline up to Month 24
measure: Percentage of Subjects Free From Expanded Disability Status Scale (EDSS) Progression at Month 12 and 24
timeFrame: Month 12 and 24
measure: Hazard Ratio for Time to First Sustained Expanded Disability Status Scale (EDSS) Progression
timeFrame: Baseline to date at which the first confirmed EDSS progression occurs, assessed up to 24 months
measure: Percentage of Subjects With Active (New/Enlarging) T2 Lesions at Month 24
timeFrame: Month 24
measure: Percentage of Subjects With Combined Unique Active (CUA) Lesions at Month 12 and 24
timeFrame: Month 12 and 24
measure: Mean Number of New Gadolinium (Gd)-Enhancing Lesions at Month 12 and 24
timeFrame: Month 12 and 24
measure: Mean Number of New T1 (Hypointense) Lesions at Month 12 and 24
timeFrame: Month 12 and 24
measure: Cumulative Number of New T1 (Hypointense) Lesions
timeFrame: Baseline up to Month 24
measure: Median Change From Baseline in Whole Brain Volume at Month 12 and 24
timeFrame: Baseline, Month 12 and 24
measure: Median Change From Baseline in Regional Brain Volume at Month 12 and 24
timeFrame: Baseline, Month 12 and 24
measure: Flu-like Symptoms (FLS) Assessed by FLS Scale Score
timeFrame: Screening, Baseline, Month 3, 6, 12 and 24
measure: Number of Subjects With Treatment Emergent Adverse Event (TEAE), Serious AE (SAE), TEAE Leading to Death and Discontinuation
timeFrame: Baseline up to Month 24
measure: Number of Subjects With Clinical Significant Abnormality in Laboratory Parameters
timeFrame: From screening up to Month 24
measure: Number of Subjects With One Concomitant Medication From Baseline up to Month 24
timeFrame: Baseline up to Month 24
measure: Time on Treatment (Adherence to Treatment)
timeFrame: Baseline up to 2.2 years
measure: Number of Subjects With Premature Termination From Treatment
timeFrame: Baseline up to Month 24
measure: Hazard Ratio for Time to First Documented Relapse
timeFrame: Baseline up to Date at which first Relapse Occurs assessed up to 24 months
Other outcomes:
Locations:
city: Naples
country: Italy
facility: Investigational Site
Study officials:
affiliation: Merck Serono S.P.A., Italy
name: Medical Responsible
role: STUDY_DIRECTOR
References:
citation: Petracca M, Quarantelli M, Moccia M, Vacca G, Satelliti B, D'Ambrosio G, Carotenuto A, Ragucci M, Assogna F, Capacchione A, Lanzillo R, Morra VB. ProspeCtive study to evaluate efficacy, safety and tOlerability of dietary supplemeNT of Curcumin (BCM95) in subjects with Active relapsing MultIple Sclerosis treated with subcutaNeous Interferon beta 1a 44 mcg TIW (CONTAIN): A randomized, controlled trial. Mult Scler Relat Disord. 2021 Nov;56:103274. doi: 10.1016/j.msard.2021.103274. Epub 2021 Sep 21.