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A Pilot Study in Subjects With Relapsing Remitting Multiple Sclerosis (RR-MS) (INCREASE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03387046
Recruitment Status : Completed
First Posted : December 29, 2017
Last Update Posted : February 21, 2019
Sponsor:
Information provided by (Responsible Party):
Merck KGaA, Darmstadt, Germany

Brief Summary:
The purpose of this study is to evaluate the improvement in spontaneous recovery from clinical deficits at the time of an acute relapse in RR-MS subjects already receiving interferon (IFN) beta 1a with D-aspartate (versus placebo) as add-on therapy.

Condition or disease Intervention/treatment Phase
Multiple Sclerosis, Relapsing-Remitting Dietary Supplement: D-aspartate Drug: Placebo Biological: IFN beta-1a Drug: Methylprednisolone Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Evaluation of clINical reCovery After a Relapse: a Pilot Study assEssing the Neuronal Effects of D-Aspartate in RR-MS Subjects Treated With IntErferon Beta 1a 44 mcg TIW (INCREASE)
Actual Study Start Date : March 26, 2018
Actual Primary Completion Date : January 11, 2019
Actual Study Completion Date : January 11, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: IFN beta-1a+Methylprednisolone+D-aspartate (MS with relapse) Dietary Supplement: D-aspartate
D-aspartate 2660 milligram (mg) once daily in the form of oral solution for 24 weeks.

Biological: IFN beta-1a
IFN beta-1a will be administered subcutaneously at a dose of 44 microgram (mcg) three times a week for 24 weeks.

Drug: Methylprednisolone
Methylprednisolone 1000 mg will be administered intravenously once daily for 5 consecutive days.

Placebo Comparator: IFN beta-1a+Methylprednisolone+Placebo (MS with relapse) Drug: Placebo
Placebo matched to D-aspartate once daily in the form of oral solution for 24 weeks.

Biological: IFN beta-1a
IFN beta-1a will be administered subcutaneously at a dose of 44 microgram (mcg) three times a week for 24 weeks.

Drug: Methylprednisolone
Methylprednisolone 1000 mg will be administered intravenously once daily for 5 consecutive days.

Experimental: IFN beta-1a+D-aspartate (MS without relapse) Dietary Supplement: D-aspartate
D-aspartate 2660 milligram (mg) once daily in the form of oral solution for 24 weeks.

Biological: IFN beta-1a
IFN beta-1a will be administered subcutaneously at a dose of 44 microgram (mcg) three times a week for 24 weeks.

Placebo Comparator: IFN beta-1a+Placebo (MS without relapse) Drug: Placebo
Placebo matched to D-aspartate once daily in the form of oral solution for 24 weeks.

Biological: IFN beta-1a
IFN beta-1a will be administered subcutaneously at a dose of 44 microgram (mcg) three times a week for 24 weeks.




Primary Outcome Measures :
  1. Percentage of Subjects With Change in Multiple Sclerosis Related Disability Measured by Functional Systems Scores of Expanded Disability Status Scale (EDSS) [ Time Frame: Week 8 ]

Secondary Outcome Measures :
  1. Percentage of Subjects With Change in Multiple Sclerosis Related Disability Measured by Functional Systems Scores of EDSS [ Time Frame: Week 12 and 24 ]
  2. Number of Subjects With Multiple Sclerosis Related Disability and Cognitive Impairment Measured by 25-foot Timed Walk (25-FWT) [ Time Frame: Week 8, 12 and 24 ]
  3. Number of Subjects With Multiple Sclerosis Related Disability and Cognitive Impairment Measured by 9 Hole Peg Test (9HPT) [ Time Frame: Week 8, 12 and 24 ]
  4. Number of Subjects With Multiple Sclerosis Related Disability and Cognitive Impairment Measured by Symbol Digit Modalities Test [ Time Frame: Week 8, 12 and 24 ]
  5. Number of Subjects With Multiple Sclerosis Related Disability and Cognitive Impairment Measured by Low Contrast Letter visual Acuity Test [ Time Frame: Week 8, 12 and 24 ]
  6. Number of Subjects With Fatigue Measured by Modified Fatigue Impact Scale (MFIS) Score [ Time Frame: Baseline, Week 8, 12 and 24 ]
  7. Number of Subjects With Fatigue Measured by Fatigue Severity Scale (FSS) Score [ Time Frame: Baseline, Week 8, 12 and 24 ]
  8. Number of Subjects With Long Term Potentiation Measured by Transcranial Magnetic Stimulation [ Time Frame: Baseline, Week 8, 12 and 24 ]
  9. Number of Treated Subjects With Immune-metabolic Response of Lymphocytes [ Time Frame: Baseline, Week 8 and 12 ]
    Immune-metabolic response of lymphocytes will be evaluated in treated subjects in vitro by Laboratory Assay.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects with RR-MS, according to the revised McDonald Criteria (2010)
  • Subjects with an expanded disability status scale (EDSS) score between 0 and 3 before screening visit and before relapse
  • Subjects receiving treatment with IFN beta 1a 44 mcg three times a week for at least 6 months but for no more than 10 years before the screening visit
  • Female subjects must be neither pregnant nor breastfeeding and must lack childbearing potential
  • Subjects willing and able to comply with the protocol for the total duration of the study
  • Subjects able to understand the purposes and the risks of the study
  • Subjects have signed the appropriate written informed consent form, approved by the Independent Ethics Committee (IEC), prior to the performance of any study activities
  • For MS subjects with relapse:
  • Deterioration of at least one step in a relevant Functional Systems Scale (FSS) or an increase in EDSS of 1 point or more compatible, according to physician's judgment, with the therapy prosecution
  • Relapse started within maximum 5 days before the inclusion in the study
  • MS subjects without relapse with clinically stable RR-MS

Exclusion Criteria:

  • Subjects with diagnosis of primary progressive MS (PP-MS)
  • Subjects have any disease other than MS that could better explain his/her signs and symptoms
  • Subjects with any comorbidity with diseases that might alter synaptic plasticity (example Parkinson Disease, Alzheimer Disease, Stroke)
  • Subjects receiving concomitant treatment with drugs that may alter synaptic plasticity (example, cannabinoids)
  • Subjects with history or presence of any unstable medical condition (tumor or chronic infection or severe life threatening infection within the last 6 months)
  • Subjects who have received any corticosteroids therapy within 3 months prior to the screening
  • Subjects with any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressive agents during the course of the study
  • Subjects who have received any immunosuppressive agents other to corticosteroids, as monotherapy or combination therapy within 3 months prior to the screening visit
  • Subjects with history or currently active primary or secondary immunodeficiency
  • Subjects with inadequate liver function, defined by alanine aminotransferase (ALT) > 3 * upper limit of normal (ULN), or alkaline phosphatase (AP) > 2 * ULN, or total bilirubin > 2 * ULN if associated with any elevation of ALT or AP
  • Subjects with inadequate bone marrow reserve, defined as a white blood cell count less than 0.5 * lower limit of normal (LLN)
  • Subjects with moderate to severe renal impairment
  • Subjects unable to complete an magnetic resonance imaging (MRI) (contraindications for MRI include but are not restricted to weight >=140 kilogram (kg), pacemaker, cochlear implants, presence of foreign substances in the eye, intracranial vascular clips, surgery within 6 weeks of entry into the study, coronary stent implanted within 8 weeks prior to the time of the intended MRI, etc)
  • Subjects with contraindication to gadolinium (Gd) can be enrolled into the study but cannot receive Gd contrast dyes during their MRI scans
  • Subjects receiving supplements that, in the Investigator's opinion, may affect the evaluation of fatigue
  • Subjects with any known contraindications or hypersensitivity to D-aspartate or any excipient
  • Subjects with any other significant disease that in the Investigator's opinion would impede study assessments or endanger the subject
  • Female subjects with positive pregnancy test at baseline or subjects with active project of pregnancy during the study
  • Subjects with legal incapacity or limited legal capacity
  • Subjects have participated in any other investigational study within 8 weeks before the screening visit

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03387046


Locations
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Italy
Ospedale Binaghi, Università di Cagliari,ASL 8
Cagliari, Italy
Ospedale Clinicizzato SS. Annunziata
Chieti, Italy
Azienda Socio Sanitaria Territoriale della Valle Olona (presidio di Gallarate)
Gallarate, Italy
Azienda Ospedaliero Universitaria San Martino
Genova, Italy
Ospedale P.A.Micone
Genova, Italy
Ospedale San Raffaele
Milano, Italy
A.O.U. Federico II
Napoli, Italy
Azienda Ospedaliera di Rilievo Nazionale A. CardarelliAzienda Ospedaliera di Rilievo Nazionale A. Cardarelli
Napoli, Italy
Seconda Università degli Studi di Napoli
Napoli, Italy
Azienda Ospedaliera di Padova
Padova, Italy
I.R.C.C.S. Neuromed-Istituto Neurologico Mediterraneo
Pozzilli, Italy
Azienda Ospedaliera San Camillo Forlanini
Roma, Italy
Azienda Ospedaliera Sant'Andrea-Università di Roma La Sapienza
Roma, Italy
Policlinico Universitario Agostino Gemelli
Roma, Italy
Azienda Ospedaliera Universitaria Policlinico Tor Vergata
Rome, Italy
Ospedale S. Paolo
Savona, Italy
Azienda Ospedaliero Universitaria Ospedali Riuniti
Torrette Di Ancona, Italy
Sponsors and Collaborators
Merck KGaA, Darmstadt, Germany
Investigators
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Study Director: Medical Responsible Merck KGaA, Darmstadt, Germany

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Responsible Party: Merck KGaA, Darmstadt, Germany
ClinicalTrials.gov Identifier: NCT03387046     History of Changes
Other Study ID Numbers: MS200136_0041
First Posted: December 29, 2017    Key Record Dates
Last Update Posted: February 21, 2019
Last Verified: February 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Merck KGaA, Darmstadt, Germany:
Relapsing remitting multiple sclerosis
D-Aspartate
interferon beta-1a

Additional relevant MeSH terms:
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N-Methylaspartate
Sclerosis
Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Interferons
Methylprednisolone Hemisuccinate
Prednisolone
Interferon-beta
Interferon beta-1a
Methylprednisolone
Methylprednisolone Acetate
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents