Effects of Dalfampridine on Cognition in Multiple Sclerosis

NCT02006160 | Completed Phase 2 Results

• 1 other identifier: NEU3270511E
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

Cognitive impairment is common in multiple sclerosis (MS) and has devastating impact on functional activities. There is great demand for medications that will enhance cognitive capacity in MS patients. To date, there is no evidence for improvement in cognition following treatment with aminopyridines, but the few studies on the topic included neuropsychological (NP) tests as secondary or tertiary outcomes, and were methodologically flawed. Dalfampridine may enhance cognition by direct pharmacological mechanisms, and should have effects on motor outcomes as in prior studies. By combining cognition and motor outcomes in the proposed study, the investigators will evaluate if the same patients with positive effects show beneficial responses on motor outcomes including physical activity and if such motor outcomes mediate and/or moderate cognitive improvements with dalfampridine

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• Symbol Digit Modalities Test

  The Symbol Digit Modalities Test is a measure of cognitive processing speed. The outcome is the total number of correct digit substitutions in 90 seconds, with a possible total range of 0-120. Higher values reflect a better score/outcome than lower scores.

  Week 0, Week 12

Study Arms (2)

treatment

ACTIVE COMPARATOR

dalfampridine

Drug: dalfampridine

control

PLACEBO COMPARATOR

placebo

Drug: placebo

Interventions

dalfampridine DRUG

10 mg bid

Also known as: Ampyra

treatment

placebo DRUG

10 mg bid

control

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Males/Females who are ≥ 18 years old and \< 65 years old and are capable of understanding and complying with the protocol, including speaking and writing fluent English and having at least a 9th grade education.
• Have a diagnosis of MS, as per revised McDonald's Criteria.
• Have not received steroids in last thirty (30) days or a relapse in the last ninety (90) days, and whose MS is considered stable.
• Impression of cognitive impairment as indicated by one of the following: (a) positive NP testing following diagnosis of MS as determined by board certified neuropsychologist or with z scores \<-1.5 below expectation in at least one cognitive domain, or (b) informant MSNQ \>28.
• An Expanded Disability Status Scale (EDSS) of ≤ 6.5.
• Have given written informed consent prior to any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to his/her future medical care.
• Are capable of performing the requirements of a NP test battery including at least 20/70 near visual acuity by near vision chart, with correction allowed.
• If female, must neither be pregnant nor breast-feeding and must either (a) be \> 12 months post-menopausal or surgically sterilized, or (b) agree to use an acceptable method of birth control for the duration of the study. Abstinence will not be considered an acceptable method of birth control.

You may not qualify if:

• Have cognitive deficits caused by concomitant medication usage or other significant neurological/psychological disease e.g. Alzheimer's disease, Parkinson's disease, stroke, transient ischemic attack, Vascular Dementia, Huntington's disease, traumatic brain injury or chronic CNS infection
• Have evidence of other medical cause(s) of cognitive impairment
• Evidence of major mental illness predating the onset of MS
• Have evidence of major depression as determined by a positive BDIFS and clinician interview
• Have report of uncontrolled or labile hypertension, tachycardia, cardiovascular or cerebrovascular disease
• History of seizure disorder.
• Optic neuritis within 6 months of enrollment.
• Trigeminal neuralgia.
• Prior exposure to aminopyridines within the last six months.

Sponsors & Collaborators

• State University of New York at Buffalo: lead

Study Sites (1)

Buffalo General Hospital

Buffalo, New York, 14203, United States

Location

Related Publications (1)

• Satchidanand N, Drake A, Smerbeck A, Hojnacki D, Kolb C, Patrick K, Weinstock-Guttman B, Motl R, Benedict RH. Dalfampridine benefits ambulation but not cognition in multiple sclerosis. Mult Scler. 2020 Jan;26(1):91-98. doi: 10.1177/1352458518815795. Epub 2018 Dec 19.

  PMID: 30566030 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

4-Aminopyridine

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Aminopyridines; Amines; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Ralph Benedict
• Organization: UBMD Neurology

benedict@buffalo.edu

7163230556

Study Officials

• Ralph Benedict, PhD

  University at Buffalo

  PRINCIPAL INVESTIGATOR

• Bianca Weinstock-Guttman, MD

  University at Buffalo

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 6, 2012
• First Posted: December 10, 2013
• Study Start: December 1, 2011
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: October 1, 2020
• Results First Posted: May 7, 2019

Record last verified: 2020-09

Locations

US (1)