Trial to look at the nerve conductance in patients with ALS, with and without Riluzole or Retigabine.

• Register: EUCTR
• Last refreshed on: 8 May 2017
• Main ID: EUCTR2015-001431-20-NL
• Date of registration: 21/04/2015
• Prospective Registration: Yes
• Primary sponsor: Centre for Human Drug Research
• Public title: Trial to look at the nerve conductance in patients with ALS, with and without Riluzole or Retigabine.
• Scientific title: A randomized, double blind, double-dummy placebo controlled, 3-way cross-over study to determine the test-retest reliability of, and the effect of oral retigabine and riluzole on, peripheral motor nerve excitability measurements in patients with ALS. - Peripheral motor nerve excitability study in patients with ALS
• Date of first enrolment: 17/08/2015
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-001431-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Netherlands

Contacts

• Name: Research Director
• Affiliation: CHDR

• Name: Research Director
• Affiliation: CHDR

Key inclusion & exclusion criteria

Inclusion criteria:
1. Ability to understand the purpose and risks of the study and provide signed and dated informed consent.
2. Aged 18 to 80 years old, inclusive, at the time of informed consent.
3. Women of childbearing potential must practice effective contraception for the duration of the study.
4. Willing to limit the intake of alcohol to no more than 2 units per day from the screening visit to the the last scheduled visit and to refrain from alcohol intake 48 hours prior to each study visit until their stay in the clinical research unit. One unit of alcohol is defined as 1 pint of beer (350 mL), 1 glass of wine (150 mL) or 1 shot of liquor (30 mL).
5. Willing to refrain from marijuana use throughout the study.
6. Willing to refrain from vigorous exercise within 48 hours prior to each study visit.
7. Must have a diagnosis of “definite”, “probable”, or “probable laboratory-supported”, ALS according to the World Federation of Neurology El Escorial criteria (revised according to the Airlie House Conference 1998 [Brooks 1999]). 8. Fasciculations in the arms observed by the treating neurologist

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 18
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. History of diabetes or neuropathy.
2. History of neuromuscular disorders (other than ALS) including but not limited to ALS mimic syndromes, myopathy, myasthenia gravis, and other motor neuron diseases.
3. Median nerve CMAP less than 1 mV.
4. Unstable cardiac, pulmonary, renal, hepatic disease or active malignancy.
5. Clinically significant abnormalities in laboratory test results as judged by the investigator. In the case of uncertain or questionable results, laboratory tests performed during the screening visit may be repeated 1 time before participation in the study to confirm eligibility or may be judged to be clinically irrelevant.
6. History or symptoms of any clinically significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and ophthalmologic or other major disease, as determined by the investigator (with the exception of the neurological syndrome listed in the inclusion criteria section).
7. 12-lead ECG demonstrating QTcB >450 msec at Screening.
8. Concomitant disease or condition that can interfere with the conduct of the study, or that in the opinion of the investigator, would pose an unacceptable risk to the subject in this study.
9. History of trauma to the upper extremities or other orthopaedic conditions that, in the opinion of the investigator, could affect the electrophysiological measurements.
10. Use of medications including but not limited to anticholinergics and muscle relaxants that, in the opinion of the investigator, could affect the electrophysiological measurements within 2 weeks prior to first dosing or within 6 times the elimination half-life of the medication prior to first dosing (whichever is longer).
11. Current enrolment in any interventional clinical study in which treatment with an investigational drug or approved therapy for investigational use is administered within 30 days prior to the screening or participation in an interventional study for an investigational drug or device within 3 months prior to Screening.
12. Pregnant, breastfeeding, or a positive pregnancy test result at Screening.
13. A positive urine test for drugs of abuse at Screening.
14. Unwillingness or inability to comply with study requirements.
15. Unspecified reasons that, in the opinion of the Investigator, make the subject unsuitable for enrollment.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Amytrophic Lateral Sclerosis
MedDRA version: 18.1 Level: PT Classification code 10002026 Term: Amyotrophic lateral sclerosis System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Trade Name: Rilutek 50 mg film-coated tablets
Product Name: Rilutek
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: RILUZOLE
CAS Number: 1744-22-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Trade Name: Trobalt
Product Name: Trobalt
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: RETIGABINE
CAS Number: 150812-12-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: To evaluate the test-retest reliability of nerve excitability threshold tracking in patients with ALS.

Secondary Objective: • To investigate the ability of Strength Duration Time Constant (SDTC) to detect effects of retigabine and riluzole in patients with ALS.
• To investigate the ability of Refractoriness at 2 ms to detect effects of retigabine and riluzole in patients with ALS.
• To investigate the ability of Superexcitability to detect effects of retigabine and riluzole in patients with ALS.
• To investigate the ability of depolarizing Threshold Electrotonus (40-60 ms)to detect effects of retigabine and riluzole in patients with ALS.
• To investigate the ability of depolarizing Threshold Electrotonus (90-100 ms) to detect effects of retigabine and riluzole in patients with ALS.
• To determine if there is a correlation between ALSFRS-R score at baseline and at 3 months and motor nerve excitability measures refractoriness at 2 ms, superexcitability, depolarizing Threshold Electrotonus (40-60 ms), depolarizing Threshold Electrotonus (90-100 ms) or Strength Duration time Constant at baseline on day 0.

Primary end point(s): • ICC for nerve excitability parameters.

Timepoint(s) of evaluation of this end point: For each occasion at pre-dose and at 1 or 2 hours post-dose and 5 or 6 hours post-dose

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: For each occasion at pre-dose and at 1 or 2 hours post-dose and 5 or 6 hours post-dose

ALSFRS-R will be taken at day 0 and at the 90 day follow-up phone-call.

POWERjar will be measured in two occasions at 4 hours post dose.

Secondary end point(s): • Axonal excitability parameters of motor axons in the median nerve.
o CMAP
o Strength Duration Time Constant (SDTC)
o Refractoriness at 2 ms
o Superexcitability
o Subexcitability
o depolarizing Threshold Electrotonus (40-60 ms)
o depolarizing Threshold Electrotonus (90-100 ms)
o hyperpolarizing Threshold Electrotonus (90-100 ms)
o Rheobase
o Hyperpolarizing I/V gradient
• Points change in ALSFRS-R scale at 3 months compared to baseline.
• Muscle strength and fatigue variables as measured with the POWERjar:
o Maximum grip strength in kilograms
o Time in seconds to reach a grip strength 10% below the maximal grip strength
o Time in seconds to reach a torque 10% (or higher, if applicable) below the predefined resistance for torque
o Time in seconds to fully release grip.

Secondary ID(s)

CHDR1417

Source(s) of Monetary Support

CHDR

Biogen Idec Ltd