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NCT01514370: CONTAIN

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

Completed Phase 2 Results posted Last updated 22 January 2019
What this trial tests

Phase 2 trial testing IFN beta 1a 44 mcg TIW in Multiple Sclerosis in 80 participants. Completed in 31 March 2016.

Timeline
30 April 2012
Primary endpoint
31 March 2016
31 March 2016

Quick facts

Lead sponsorMerck KGaA, Darmstadt, Germany
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment80
Start date30 April 2012
Primary completion31 March 2016
Estimated completion31 March 2016
Sites1 location across Italy

Drugs / interventions tested

Conditions studied

Sponsor

Merck KGaA, Darmstadt, Germany — full company profile →

Who can join

Adults 18 to 60, any sex, with Multiple Sclerosis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

GroupValue95% CI
IFN Beta 1a 44 mcg TIW + Curcumin (BCM95)4
IFN Beta 1a 44 mcg TIW + Placebo7
Percentage of Relapse-Free Subjects at Month 12 and Month 24 Secondary · 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.

Month 12
GroupValue95% CI
IFN Beta 1a 44 mcg TIW + Curcumin (BCM95)75.0
IFN Beta 1a 44 mcg TIW + Placebo67.5
Month 24
GroupValue95% CI
IFN Beta 1a 44 mcg TIW + Curcumin (BCM95)60.0
IFN Beta 1a 44 mcg TIW + Placebo50.0
Annualized Relapse Rate at Month 12 and 24 Secondary · 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.

Month 12
GroupValue95% CI
IFN Beta 1a 44 mcg TIW + Curcumin (BCM95)1.73± 0.70
IFN Beta 1a 44 mcg TIW + Placebo1.40± 0.65
Month 24
GroupValue95% CI
IFN Beta 1a 44 mcg TIW + Curcumin (BCM95)1.05± 0.73
IFN Beta 1a 44 mcg TIW + Placebo1.14± 0.82
Total Number of Reported Relapses at Month 3, 6, 12 and 24 Secondary · 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.

Month 3
GroupValue95% CI
IFN Beta 1a 44 mcg TIW + Curcumin (BCM95)1.00± 0.00
IFN Beta 1a 44 mcg TIW + Placebo1.00± 0.00
Month 6
GroupValue95% CI
IFN Beta 1a 44 mcg TIW + Curcumin (BCM95)1.00± 0.00
IFN Beta 1a 44 mcg TIW + Placebo1.00± NA
Month 12
GroupValue95% CI
IFN Beta 1a 44 mcg TIW + Curcumin (BCM95)1.50± 0.58
IFN Beta 1a 44 mcg TIW + Placebo1.00± 0.00
Month 24
GroupValue95% CI
IFN Beta 1a 44 mcg TIW + Curcumin (BCM95)1.57± 0.79
IFN Beta 1a 44 mcg TIW + Placebo1.75± 0.96
Percentage of Subjects Treated With Glucocorticoids Due to Relapses During 24 Months Secondary · Baseline up to 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. Percentage of subjects treated with glucocorticoids due to relapses during 24 Months were reported here.

GroupValue95% CI
IFN Beta 1a 44 mcg TIW + Curcumin (BCM95)30.0
IFN Beta 1a 44 mcg TIW + Placebo35.0
Percentage of Subjects Free From Expanded Disability Status Scale (EDSS) Progression at Month 12 and 24 Secondary · 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

Month 12
GroupValue95% CI
IFN Beta 1a 44 mcg TIW + Curcumin (BCM95)92.5
IFN Beta 1a 44 mcg TIW + Placebo82.5
Month 24
GroupValue95% CI
IFN Beta 1a 44 mcg TIW + Curcumin (BCM95)90.0
IFN Beta 1a 44 mcg TIW + Placebo85.0
Hazard Ratio for Time to First Sustained Expanded Disability Status Scale (EDSS) Progression Secondary · Baseline to date at which the first confirmed EDSS progression occurs, assessed up to 24 months

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 t

GroupValue95% CI
IFN Beta 1a 44 mcg TIW + [Curcumin (BCM95) and Placebo]0.3090.023 – 4.115
Percentage of Subjects With Active (New/Enlarging) T2 Lesions at Month 24 Secondary · 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.

GroupValue95% CI
IFN Beta 1a 44 mcg TIW + Curcumin (BCM95)20.0
IFN Beta 1a 44 mcg TIW + Placebo17.5
Percentage of Subjects With Combined Unique Active (CUA) Lesions at Month 12 and 24 Secondary · 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.

Month 12
GroupValue95% CI
IFN Beta 1a 44 mcg TIW + Curcumin (BCM95)7.5
IFN Beta 1a 44 mcg TIW + Placebo17.5
Month 24
GroupValue95% CI
IFN Beta 1a 44 mcg TIW + Curcumin (BCM95)15.0
IFN Beta 1a 44 mcg TIW + Placebo12.5
Mean Number of New Gadolinium (Gd)-Enhancing Lesions at Month 12 and 24 Secondary · Month 12 and 24

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

Month 12
GroupValue95% CI
IFN Beta 1a 44 mcg TIW + Curcumin (BCM95)0.19± 0.79
IFN Beta 1a 44 mcg TIW + Placebo0.46± 1.61
Month 24
GroupValue95% CI
IFN Beta 1a 44 mcg TIW + Curcumin (BCM95)0.21± 0.63
IFN Beta 1a 44 mcg TIW + Placebo0.13± 0.63
Mean Number of New T1 (Hypointense) Lesions at Month 12 and 24 Secondary · 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.

Month 12
GroupValue95% CI
IFN Beta 1a 44 mcg TIW + Curcumin (BCM95)0.52± 1.28
IFN Beta 1a 44 mcg TIW + Placebo0.48± 1.87
Month 24
GroupValue95% CI
IFN Beta 1a 44 mcg TIW + Curcumin (BCM95)0.19± 0.68
IFN Beta 1a 44 mcg TIW + Placebo0.04± 0.21
Cumulative Number of New T1 (Hypointense) Lesions Secondary · Baseline up to Month 24

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

GroupValue95% CI
IFN Beta 1a 44 mcg TIW + Curcumin (BCM95)0.58± 1.32
IFN Beta 1a 44 mcg TIW + Placebo0.39± 1.64

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline up to Month 24. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

IFN Beta 1a 44 mcg TIW + Curcumin (BCM95)
Serious: 1/38 (3%)
Deaths:
IFN Beta 1a 44 mcg TIW + Placebo
Serious: 0/40 (0%)
Deaths:

Serious adverse events (1 terms)

ReactionSystemIFN Beta 1a 44 mcg TIW + C…IFN Beta 1a 44 mcg TIW + P…
Eye abscessInfections and infestations
Other adverse events (48 terms — click to expand)

ReactionSystemIFN Beta 1a 44 mcg TIW + C…IFN Beta 1a 44 mcg TIW + P…
Urinary retentionRenal and urinary disorders
Abdominal discomfortGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
HeadacheNervous system disorders
DepressionPsychiatric disorders
Astringent therapySurgical and medical procedures
LymphadenopathyBlood and lymphatic system disorders
Ear painEar and labyrinth disorders
VertigoEar and labyrinth disorders
Autoimmune thyroiditisEndocrine disorders
ThyroiditisEndocrine disorders
DiplopiaEye disorders
ScotomaEye disorders
Abdominal distensionGastrointestinal disorders
ConstipationGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
ToothacheGastrointestinal disorders
DyspepsiaGastrointestinal disorders
Chest painGeneral disorders
CystGeneral disorders
FatigueGeneral disorders
Oedema peripheralGeneral disorders
CystitisInfections and infestations
InfluenzaInfections and infestations
Venous injuryInjury, poisoning and procedural complications
Gamma-glutamyltransferase increasedInvestigations
Decreased appetiteMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
MyalgiaMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
HypoaesthesiaNervous system disorders
MigraineNervous system disorders
Multiple sclerosis relapseNervous system disorders
Muscle spasticityNervous system disorders
ParaesthesiaNervous system disorders
Trigeminal neuralgiaNervous system disorders
Cystitis noninfectiveRenal and urinary disorders
NephrolithiasisRenal and urinary disorders
Urinary incontinenceRenal and urinary disorders

Most-reported serious reactions: Eye abscess.

Data from ClinicalTrials.gov NCT01514370 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Targeting oxidative stress in disease: promise and limitations of antioxidant therapy.
    Forman HJ, Zhang H. · · 2021 · cited 1789× · PMID 34194012 · DOI 10.1038/s41573-021-00233-1
  2. Are Astrocytes the Predominant Cell Type for Activation of Nrf2 in Aging and Neurodegeneration?
    Liddell JR. · · 2017 · cited 114× · PMID 28820437 · DOI 10.3390/antiox6030065
  3. Manganese superoxide dismutase in cancer prevention.
    Robbins D, Zhao Y. · · 2014 · cited 62× · PMID 23706068 · DOI 10.1089/ars.2013.5297
  4. Dietary interventions for multiple sclerosis-related outcomes.
    Parks NE, Jackson-Tarlton CS, Vacchi L, Merdad R, et al · · 2020 · cited 57× · PMID 32428983 · DOI 10.1002/14651858.cd004192.pub4
  5. Targeting NLRP3 Inflammasome With Nrf2 Inducers in Central Nervous System Disorders.
    Tastan B, Arioz BI, Genc S. · · 2022 · cited 56× · PMID 35418995 · DOI 10.3389/fimmu.2022.865772
  6. Therapeutic Potential of Curcumin for the Treatment of Brain Tumors.
    Klinger NV, Mittal S. · · 2016 · cited 52× · PMID 27807473 · DOI 10.1155/2016/9324085
  7. Phytochemicals as inhibitors of tumor necrosis factor alpha and neuroinflammatory responses in neurodegenerative diseases.
    Zahedipour F, Hosseini SA, Henney NC, Barreto GE, et al · · 2022 · cited 40× · PMID 35017414 · DOI 10.4103/1673-5374.332128
  8. Manipulating Macrophage/Microglia Polarization to Treat Glioblastoma or Multiple Sclerosis.
    Kuntzel T, Bagnard D. · · 2022 · cited 33× · PMID 35214076 · DOI 10.3390/pharmaceutics14020344

Verify or expand the search:

Other recruiting trials for Multiple Sclerosis

Currently open trials in the same condition.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01514370.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing