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Multiple SclerosisPhase 2CONTAINNCT01514370

Dietary Supplement of Curcumin in Subjects With Active Relapsing Multiple Sclerosis Treated With Subcutaneous Interferon Beta 1a

A Phase 2 study testing IFN beta 1a 44 mcg TIW and Curcumin in people with Multiple Sclerosis, run by Merck KGaA, Darmstadt, Germany at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 60 years
Conditions the study is for
Multiple Sclerosis
What is being tested?
IFN beta 1a 44 mcg TIW and Curcumin
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
80 participants
Where
1 siteItaly
Study dates
30 Apr 2012to 31 Mar 2016
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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

Who cannot join

  • 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.
Show all 13Show fewer
  • 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)

Trial locations and contacts

1 site in 1 country.

Italy1 site
  • Investigational Site

    Naples, 80131

Other trials in Italy

About this study

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)

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.

Read the 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).

Being tested
IFN beta 1a 44 mcg TIW, Curcumin, Placebo
Keywords
Multiple Sclerosis, Relapsing, Interferon beta 1a, Curcumin
Medical subject headings
Multiple Sclerosis, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IFN beta 1a 44 mcg TIWDrug

    Also called Interferon beta 1a

    Subjects received IFN beta 1a 44 microgram (mcg) subcutaneously TIW for 24 months.

  • CurcuminDrug

    Also called Rebif, BCM95

    Subjects received 500 milligram (mg) curcumin orally twice a day for 24 months.

  • PlaceboDrug

    Subjects received placebo matched to curcumin orally twice a day for 24 months.

Study groups in NCT01514370
Study groupRoleWhat they receive
IFN beta 1a 44 mcg TIW + curcumin (BCM95)ExperimentalNot described
Receives: Drug: IFN beta 1a 44 mcg TIW; Drug: Curcumin
IFN beta 1a 44 mcg TIW + placeboPlacebo comparatorNot described
Receives: Drug: IFN beta 1a 44 mcg TIW; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Subjects With Active (New or Enlarging) T2 Lesions Assessed by Magnetic Resonance Imaging (MRI) at Month 12

    A single T2 lesion was defined as an area of increased signal on a given 3-millimeters axial image that was not referable to normally hyperintense structures. New T2 lesions were those that appear in areas where on the previous scan no abnormality was detected. All T2 lesions were detected by an MRI scan.

    Measured: Month 12

Secondary outcomes (20)
  1. Percentage of Relapse-Free Subjects at Month 12 and Month 24

    Relapse was defined as the development of new or the exacerbation of existing neurological symptoms or signs, in the absence of fever, lasting for 24 hours and with a previous period for more than 30 days with a stable or an improving condition.

    Measured: Month 12 and 24

  2. Annualized Relapse Rate at Month 12 and 24

    Relapse was defined as the development of new or the exacerbation of existing neurological symptoms or signs, in the absence of fever, lasting for 24 hours and with a previous period for more than 30 days with a stable or an improving condition. Annualized relapse rate was calculated by dividing the total number of relapse events by the total number of days subjects participated in the study. This number was then multiplied by 365.25 to get an annualized rate.

    Measured: Month 12 and 24

  3. Total Number of Reported Relapses at Month 3, 6, 12 and 24

    Relapse was defined as the development of new or the exacerbation of existing neurological symptoms or signs, in the absence of fever, lasting for 24 hours and with a previous period for more than 30 days with a stable or an improving condition.

    Measured: Month 3, 6, 12 and 24

  4. Percentage of Subjects Treated With Glucocorticoids Due to Relapses During 24 Months

    Relapse was defined as the development of new or the exacerbation of existing neurological symptoms or signs, in the absence of fever, lasting for 24 hours and with a previous period for more than 30 days with a stable or an improving condition. Percentage of subjects treated with glucocorticoids due to relapses during 24 Months were reported here.

    Measured: Baseline up to Month 24

  5. Percentage of Subjects Free From Expanded Disability Status Scale (EDSS) Progression at Month 12 and 24

    Disability progression was assessed using EDSS. EDSS is based on a standardized neurological exam and focuses on symptoms that commonly occur in multiple sclerosis (MS) . Overall scores ranges from 0.0 (normal) to 10.0 (death due to MS). Disability progression was defined as an increase of EDSS score of at least 1.0 point compared to baseline for subjects with an EDSS =< 4.0. For subjects with an EDSS= 0 at baseline, EDSS progression was defined as an increase of EDSS score of at least 1.5 point. Percentage of subjects free from EDSS progression at Month 12 and 24 were reported

    Measured: Month 12 and 24

  6. Hazard Ratio for Time to First Sustained Expanded Disability Status Scale (EDSS) Progression

    EDSS progression is based on a standardized neurological exam and focuses on symptoms that commonly occur in MS. Overall scores ranges from 0.0 (normal) to 10.0 (death due to MS). A sustained progression on EDSS score was defined as an EDSS progression confirmed into two consecutive assessment. EDSS values obtained during clinical attacks are not excluded for the assessment of EDSS progression. However, EDSS values obtained during MS attacks that are not confirmed after two consecutive assessments will be excluded from statistical analysis of confirmed EDSS progression. Hazard ratio for time to first sustained EDSS progression was planned to be reported as per SAP.

    Measured: Baseline to date at which the first confirmed EDSS progression occurs, assessed up to 24 months

  7. Percentage of Subjects With Active (New/Enlarging) T2 Lesions at Month 24

    A single T2 lesion was defined as an area of increased signal on a given 3-millimeters axial image that was not referable to normally hyperintense structures. New T2 lesions were those that appear in areas where on the previous scan no abnormality was detected. All T2 lesions were detected by an MRI scan.

    Measured: Month 24

  8. Percentage of Subjects With Combined Unique Active (CUA) Lesions at Month 12 and 24

    CUA lesion was defined as new gadolinium (Gd)-enhancing lesions on T1-weighted, or new or enlarging lesions on T2-weighted MRI scans, without double counting.

    Measured: Month 12 and 24

  9. Mean Number of New Gadolinium (Gd)-Enhancing Lesions at Month 12 and 24

    New Gd-enhancing Lesions are a measure of inflammatory activity and were assessed using the Magnetic Resonance Imaging (MRI) scan.

    Measured: Month 12 and 24

  10. Mean Number of New T1 (Hypointense) Lesions at Month 12 and 24

    Mean number of new T1 (Hypointense) Lesions represents a measure of accumulation of inflammatory disease burden assessed on magnetic resonance imaging (MRI) scans.

    Measured: Month 12 and 24

  11. Cumulative Number of New T1 (Hypointense) Lesions

    Cumulative number of new T1 (Hypointense) lesions were reported.

    Measured: Baseline up to Month 24

  12. Median Change From Baseline in Whole Brain Volume at Month 12 and 24

    Brain tissue volumes are inter-related and represent a measure of neurodegenerative aspects of the disease.

    Measured: Baseline, Month 12 and 24

  13. Median Change From Baseline in Regional Brain Volume at Month 12 and 24

    Brain tissue volumes are inter-related and represent a measure of neurodegenerative aspects of the disease.

    Measured: Baseline, Month 12 and 24

  14. Flu-like Symptoms (FLS) Assessed by FLS Scale Score

    Flu-like symptoms were measured using FLS score in which subjects were scored as per the presence and intensity of muscle aches, chills, and weakness, each separately, on a scale of 0-3 as follows: 0 = absent; 1 = mild, do not interfere with daily activities; 2 = moderate, sufficient to interfere with daily activities; and 3 = severe, bed rest require. Body temperature also was also recorded to determine the presence of fever using the following scale: 0 (≤ 37.2 °C); 1 (≥ 37.3 °C but < 37.8 °C); 2 (≥ 37.8 but < 38.4 °C); and 3 (≥ 38.4 °C).The scores for each symptom (muscle aches, chills, weakness, body temperature) was added together to provide the combined flu-like symptom score ranging from 0 to 12 where 0 indicates absence of any symptom and 12 indicates the worst severity of the symptoms.

    Measured: Screening, Baseline, Month 3, 6, 12 and 24

  15. Number of Subjects With Treatment Emergent Adverse Event (TEAE), Serious AE (SAE), TEAE Leading to Death and Discontinuation

    AE was defined as any untoward medical occurrence which does not necessarily have a causal relationship with the study drug. An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent are events between first dose of study drug and up to 24 months. TEAEs include both Serious TEAEs and non-serious TEAEs.

    Measured: Baseline up to Month 24

  16. Number of Subjects With Clinical Significant Abnormality in Laboratory Parameters

    Laboratory assessment included haematology, chemistry, and urinalysis. Clinical significance was determined by the investigator.

    Measured: From screening up to Month 24

  17. Number of Subjects With One Concomitant Medication From Baseline up to Month 24

    Number of subjects with at least one concomitant medication from baseline up to month 24 were reported.

    Measured: Baseline up to Month 24

  18. Time on Treatment (Adherence to Treatment)

    Time up to which subjects were adhered to the treatment was reported.

    Measured: Baseline up to 2.2 years

  19. Number of Subjects With Premature Termination From Treatment

    Number of subjects with premature termination from treatment were reported.

    Measured: Baseline up to Month 24

  20. Hazard Ratio for Time to First Documented Relapse

    Relapse was defined as the development of new or the exacerbation of existing neurological symptoms or signs, in the absence of fever, lasting for 24 hours and with a previous period for more than 30 days with a stable or an improving condition. Hazard ratio for time to first documented relapse was planned to be reported as per SAP.

    Measured: Baseline up to Date at which first Relapse Occurs assessed up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Jan 2012 (estimated)
  2. Study start30 Apr 2012
  3. Primary completion31 Mar 2016
  4. Study completion31 Mar 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
80 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01514370
Sponsor's protocol ID
EMR200136-549
Acronym
CONTAIN
Status last verified
Aug 2018
First submitted
17 Jan 2012
Last updated
22 Jan 2019

Publications

  • 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.

    PubMed 34583214

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing IFN beta 1a 44 mcg TIW and Curcumin in people with Multiple Sclerosis, run by Merck KGaA, Darmstadt, Germany at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Subjects With Active (New or Enlarging) T2 Lesions Assessed by Magnetic Resonance Imaging (MRI) at Month 12 (time frame: Month 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01514370, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2019.

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