Treatment of Pendular Nystagmus in OPT

Treatment of Pendular Nystagmus With Gabapentin and Memantine in Patients With Oculopalatal Tremor: a Controled Open-label Study

Pendular nystagmus corresponds to an enduring to and fro eye oscillation without resetting quick phases. The most common causes of acquired pendular nystagmus (APN) are multiple sclerosis (MS) and focal brainstem lesions (oculopalatal tremor, OPT). Based on pathophysiological hypothesis, pharmacological treatments of acquired nystagmus have been thoroughly proposed over different publications of cases, series, reviews or expert opinions. Acquired pendular nystagmus underwent the most rigorous treatment trials, leading to the proposal of gabapentin or memantine as valuable drugs. Whether gabapentin and memantine are effective in APN associated with OPT remains unclear, since none of the previous studies has evaluated the effect of these medications in a group of OPT patients. However, this is an important issue in prospect to a clinical use of these medications. In the current study, the investigators aim is to evaluate the effect of gabapentin and memantine on the mean velocity, amplitude and frequency of pendular nystagmus, as well as on visual acuity and vision-specific health-related quality of life score, in a group of OPT patients

Study Overview

• Status: Completed
• Conditions: Pendular Nystagmus; Oculopalatal Tremor
• Intervention / Treatment: Drug: Gabapentin; Drug: Memantine

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Lyon, France, 69002
    • Hospices Civils de Lyon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with a diagnosis of oculopalatal tremor (OPT), following a focal brainstem lesion.
• All patients may present a chronic acquired pendular nystagmus due to OPT, observed over a period of 6 months.
• All patients will be informed about the design and purpose of the study, and all will give their informed, written consent to the protocol, which may have been approved by the local ethics committee.
• Age: above 18
• Able to understand the instructions
• Having a health coverage
• Able to sit down for 1 hour
• Stable dosage of previous medications (beginning 3 weeks previously and terminating at the end of the trial duration), except gabapentin or memantine.
• For women: efficient contraception during the experimental time and in the two month following treatment withdrawal.

Exclusion Criteria:

• Ophthalmological

  • Other ophthalmological disorder that could impair corrected visual acuity (Maculopathy, Retinopathy…)

• Neurological

  • Ongoing seizure
  • Severe handicap that does not allow sitting down position for 1 hour
• Suicidal behavior or risk

• Treatment

  • Under memantine or gabapentin medication (these medications should have been stopped for at least 1 week for gabapentin and 3 weeks for memantine)
  • Under morphine, N-methyl-D-aspartate such as amantadine, ketamine or dextromethorphan
  • Steroid medication for a current relapse (beginning 3 weeks previously and terminating at the end of the trial duration
  • Known hypersensitivity to memantine or gabapentin

• General

  • Unstable medical state
  • Patient with a galactose intolerance, a lapp lactase deficiency or glucose-galactose malabsorption
  • Moderate renal failure (creatinine clearance < 50 mL/min on bioassay dated from less than one month)
  • Recent heart infarction (<3months)
  • Unstable congestive heart insufficiency
  • Unstable arterial hypertension
  • Leucopenia (<2500/mm3)
  • Transaminase increase (>5 time normal values)
• Pregnancy (on questioning)
• Tutelage or any legal protection measure

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: memantine first; Patients will be randomly assigned to start on either memantine or gabapentin. For tolerance reasons, each treatment begins with a progressive increasing dose and stops with a progressive decreasing dose. The duration of the period of last dose (8 to 11 days) will be chosen according to the investigator's availability to organize post-tests.	Drug: Memantine
Experimental: gabapentin first; Patients will be randomly assigned to start on either memantine or gabapentin. For tolerance reasons, each treatment begins with a progressive increasing dose and stops with a progressive decreasing dose. The duration of the period of last dose (8 to 11 days) will be chosen according to the investigator's availability to organize post-tests.	Drug: Gabapentin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Velocity, amplitude and frequency of nystagmus using eye movement recording	at Day 17-21
Velocity, amplitude and frequency of nystagmus using eye movement recording	at Day 34-42
Velocity, amplitude and frequency of nystagmus using eye movement recording	at Day 64-79
Velocity, amplitude and frequency of nystagmus using eye movement recording	at Day 81-100

Secondary Outcome Measures

Outcome Measure	Time Frame
Functional score on questioning as measured by the 25-Item National Eye Institute Visual Function Questionnaire	at Day 17-21
Functional score on questioning as measured by the 25-Item National Eye Institute Visual Function Questionnaire	at Day 34-42
Functional score on questioning as measured by the 25-Item National Eye Institute Visual Function Questionnaire	at Day 64-79
Functional score on questioning as measured by the 25-Item National Eye Institute Visual Function Questionnaire	at Day 81-100
subjective measure of oscillopsia	at Day 17-21
subjective measure of oscillopsia	at Day 34-42
subjective measure of oscillopsia	at Day 64-79
subjective measure of oscillopsia	at Day 81-100
far visual acuity as measured by monocularly and binocularly direction and amplitude (measures in degrees) of their oscillopsia while viewing, with best correction, a stationary target at far (5 m) and near (57 cm) location.	at Day 17-21
far visual acuity as measured by monocularly and binocularly direction and amplitude (measures in degrees) of their oscillopsia while viewing, with best correction, a stationary target at far (5 m) and near (57 cm) location.	at Day 34-42
far visual acuity as measured by monocularly and binocularly direction and amplitude (measures in degrees) of their oscillopsia while viewing, with best correction, a stationary target at far (5 m) and near (57 cm) location.	at Day 64-79
far visual acuity as measured by monocularly and binocularly direction and amplitude (measures in degrees) of their oscillopsia while viewing, with best correction, a stationary target at far (5 m) and near (57 cm) location.	at Day 81-100

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Caroline Tilikete, Pr, Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: May 22, 2015
• First Submitted That Met QC Criteria: June 4, 2015
• First Posted (Estimate): June 9, 2015

Study Record Updates

• Last Update Posted (Actual): July 11, 2018
• Last Update Submitted That Met QC Criteria: July 10, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: multiple sclerosis; nystagmus; pharmacological trial; oscillopsia
• Additional Relevant MeSH Terms: Nervous System Diseases; Eye Diseases; Neurologic Manifestations; Dyskinesias; Cranial Nerve Diseases; Ocular Motility Disorders; Tremor; Nystagmus, Pathologic; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Tranquilizing Agents; Psychotropic Drugs; Dopamine Agents; Anti-Anxiety Agents; Anticonvulsants; Antimanic Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Gabapentin; Memantine
• Other Study ID Numbers: 69HCL14_0438; 2014-005548-17 (EudraCT Number)