Clinical trial NCT03387046: A Pilot Study in Participants With Relapsing Remitting Multiple Sclerosis (RR-MS)
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Multiple Sclerosis, Relapsing-Remitting
Keywords: Relapsing remitting multiple sclerosis
D-Aspartate
interferon beta-1a
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2017-12-29
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: Inclusion Criteria:

* Participants with RR-MS, according to the revised McDonald Criteria (2010)
* Participants with an expanded disability status scale (EDSS) score between 0 and 3 before screening visit and before relapse
* Participants 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 participants must be neither pregnant nor breastfeeding and must lack childbearing potential
* Participants willing and able to comply with the protocol for the total duration of the study
* Participants able to understand the purposes and the risks of the study
* Participants 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 participants 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 participants without relapse with clinically stable RR-MS

Exclusion Criteria:

* Participants with diagnosis of primary progressive MS (PP-MS)
* Participants have any disease other than MS that could better explain his/her signs and symptoms
* Participants with any comorbidity with diseases that might alter synaptic plasticity (example Parkinson Disease, Alzheimer Disease, Stroke)
* Participants receiving concomitant treatment with drugs that may alter synaptic plasticity (example, cannabinoids)
* Participants with history or presence of any unstable medical condition (tumor or chronic infection or severe life threatening infection within the last 6 months)
* Participants who have received any corticosteroids therapy within 3 months prior to the screening
* Participants with any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressive agents during the course of the study
* Participants who have received any immunosuppressive agents other to corticosteroids, as monotherapy or combination therapy within 3 months prior to the screening visit
* Participants with history or currently active primary or secondary immunodeficiency
* Participants 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
* Participants with inadequate bone marrow reserve, defined as a white blood cell count less than 0.5 \* lower limit of normal (LLN)
* Participants with moderate to severe renal impairment
* Participants 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)
* Participants with contraindication to gadolinium (Gd) can be enrolled into the study but cannot receive Gd contrast dyes during their MRI scans
* Participants receiving supplements that, in the Investigator's opinion, may affect the evaluation of fatigue
* Participants with any known contraindications or hypersensitivity to D-aspartate or any excipient
* Participants with any other significant disease that in the Investigator's opinion would impede study assessments or endanger the participant
* Female participants with positive pregnancy test at baseline or participants with active project of pregnancy during the study
* Participants with legal incapacity or limited legal capacity
* Participants have participated in any other investigational study within 8 weeks before the screening visit

Primary outcomes:
measure: Number of Participants With Change From Baseline in Multiple Sclerosis Related Disability Measured by Expanded Disability Status Scale (EDSS) at Week 8
timeFrame: Baseline, Week 8
Secondary outcomes:
measure: Number of Participants With Change From Baseline in Multiple Sclerosis Related Disability Measured by Expanded Disability Status Scale (EDSS) at Week 12 and 24
timeFrame: Baseline, Week 12 and 24
measure: 25-foot Timed Walk (25-FWT) to Measure Multiple Sclerosis Related Disability and Cognitive Impairment
timeFrame: At Week 8, 12 and 24
measure: 9 Hole Peg Test (9HPT) to Measure Multiple Sclerosis Related Disability and Cognitive Impairment
timeFrame: Week 8, 12 and 24
measure: Symbol Digit Modalities Test to Measure Multiple Sclerosis Related Disability and Cognitive Impairment
timeFrame: At Week 8, 12 and 24
measure: Low Contrast Letter Visual Acuity Test to Measure Multiple Sclerosis Related Disability and Cognitive Impairment
timeFrame: Week 8, 12 and 24
measure: Modified Fatigue Impact Scale (MFIS) Score to Measure Fatigue at Week 8, 12 and 24
timeFrame: Week 8, 12 and 24
measure: Fatigue Severity Scale (FSS) Score to Measure Fatigue by at Week 8, 12 and 24
timeFrame: Week 8, 12 and 24
measure: Long Term Potentiation Measured by Transcranial Magnetic Stimulation (TMS)
timeFrame: Baseline (0 minute) and Post-Baseline (15 minutes) at Week 8
measure: Number of Treated Participants With Immune-metabolic Response of Lymphocytes
timeFrame: Baseline, Week 8 and 12
Other outcomes:
Locations:
city: Cagliari
country: Italy
facility: Ospedale Binaghi, Università di Cagliari,ASL 8
city: Chieti
country: Italy
facility: Ospedale Clinicizzato SS. Annunziata
city: Gallarate
country: Italy
facility: Azienda Socio Sanitaria Territoriale della Valle Olona (presidio di Gallarate)
city: Genova
country: Italy
facility: Azienda Ospedaliero Universitaria San Martino
city: Genova
country: Italy
facility: Ospedale P.A.Micone
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Napoli
country: Italy
facility: A.O.U. Federico II
city: Napoli
country: Italy
facility: Azienda Ospedaliera di Rilievo Nazionale A. CardarelliAzienda Ospedaliera di Rilievo Nazionale A. Cardarelli
city: Napoli
country: Italy
facility: Seconda Università degli Studi di Napoli
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Pozzilli
country: Italy
facility: I.R.C.C.S. Neuromed-Istituto Neurologico Mediterraneo
city: Roma
country: Italy
facility: Azienda Ospedaliera San Camillo Forlanini
city: Roma
country: Italy
facility: Azienda Ospedaliera Sant'Andrea-Università di Roma La Sapienza
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli
city: Rome
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Tor Vergata
city: Savona
country: Italy
facility: Ospedale S. Paolo
city: Torrette Di Ancona
country: Italy
facility: Azienda Ospedaliero Universitaria Ospedali Riuniti
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: