A Registry-Based Clinical Trial of Pimozide in Patients With Neuromuscular Junction Transmission Dysfunction Due to ALS

NCT02463825 | Unknown Phase 2

• 1 other identifier: REB14-0617
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Amyotrophic lateral sclerosis (ALS) is a neuromuscular disease that results in rapid decline in normal muscle function and tone leading to difficulties with mobility, eating, drinking, breathing, sleeping, and communicating. The disease is progressive and no cure currently exists. Most people diagnosed with ALS succumb within 3 to 5 years. The only approved treatment to slow the progression of ALS is called Rilutek® (riluzole) which has only a modest effect and has been shown to increase survival by a few months. Muscular dysfunction present in people with ALS is caused by nerve breakdown and a dysfunction in the communication between the muscles and the nerves. The area where these communications occur is called the neuromuscular junction. Some recent studies have focused on using different medications to enhance communication at the neuromuscular junction with the goal of improving muscle function as a result. This approach is unproven but may help to slow the progression of the disease. Pimozide is a medication that has been demonstrated to enhance communication at the neuromuscular junction in fish and mice. This study will look at whether Pimozide may help to slow the progression of ALS and how much medication needs to be taken to have an effect.

Conditions

Amyotrophic Lateral Sclerosis (ALS)

Outcome Measures

Primary Outcomes (3)

• ALS Functional Rating Scale-Revised (ALSFRS-R)

  A questionnaire based rating scale that assesses the functioning of ALS subjects across 4 domains: gross motor activity, fine motor activity, bulbar, and respiratory function

  Change from randomization in ALSRSR-R at visit 5(day 51) and change from randomization in ALSFRS-R at visit 6 (day 65)

• Slow Vital Capacity (SVC)

  SVC will be measured using a spirometer.

  Change from screen (day -14) and randomization (day 1) in SVC at visit 5 (day 51), and Change from screen (day -14) and randomization (day 1) in SVC at visit 6 (day 65)

• Decremental responses on repetitive nerve stimulation (DRRNS)

  Using Caldwell Electromyographic System, perform repetitive nerve stimulation studies and estimates of amplitude of decremental responses.

  Change from screen (day -14) and randomization (day 1) in DRRNS at visit 5 (day 51), and Change from screen (day -14) and randomization (day 1) in DRRNS at visit 6 (day 65)

Secondary Outcomes (1)

• Adverse Effects

  Day 12, visit 3 (day 23), visit 4 (day 36), visit 5 (day 51), and visit 6 (day 65).

Study Arms (3)

Group 1 Pimozide (2mg per day)

EXPERIMENTAL

Pimozide will be initiated at 1 mg twice daily and maintained on 2mg/day for 50 days. End of study dose reduction will begin following the Final Outcome Measure Visit (Day 65). Pimozide will then be stopped.

Drug: Pimozide 2 mg per day

Group 2 Pimozide (4mg per day)

EXPERIMENTAL

Pimozide will be initiated at 1 mg twice daily then increased by 1mg twice daily every five days to 4 mg/day) for 45 days. End of study dose reduction will begin following the Final Outcome Measure Visit (Day 65). Pimozide will be titrated by reducing the dose by 1 mg twice daily every day to full discontinuation (over 2 days).

Drug: Pimozide 4 mg per day

Group 3 Placebo (Lactose tablet)

PLACEBO COMPARATOR

Placebo tablets will be utilized and administered in an identical manner for subjects in Group 3

Drug: Placebo (Lactose tablet)

Interventions

Pimozide 2 mg per day DRUG

Group 1 Pimozide (2mg per day)

Pimozide 4 mg per day DRUG

Group 2 Pimozide (4mg per day)

Placebo (Lactose tablet) DRUG

Group 3 Placebo (Lactose tablet)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients classified as having clinically definite, clinically probable, or clinically probable (laboratory-supported) ALS according to the El-Escorial diagnostic criteria for ALS
• Evidence of decremental response greater or equal to 5.0% in at least one nerve-muscle pair at the initial screening visit
• Age 18 years or greater
• Consent to participate in the Canadian Neuromuscular Disease Registry (CNDR) (follow-up study component only).

You may not qualify if:

• Diagnosis of clinically possible or clinically suspected ALS as defined by the El-Escorial diagnostic criteria for ALS
• If the subject is taking riluzole the dose must be stable for 30 days prior to randomization visit. Riluzole cannot be initiated during the study.
• History of Parkinson's disease
• History of traumatic brain injury
• History of neuroleptic malignant syndrome
• History of hypersensitivity or serious adverse reaction(s) to a neuroleptic medication
• History of prolonged QTc interval \> 500 ms
• History of hyponatremia \< 130 mmol/L
• History of current heparin or warfarin use
• History of hepatic and/or renal impairment that may affect pimozide metabolism
• History of current pregnancy or breastfeeding
• Current antipsychotic use
• Presence of central nervous system depression, comatose states, liver disorders, renal insufficiency, and blood dyscrasias
• Presence of depressive disorders or Parkinson's syndrome
• History of congenital long QT syndrome or with a family history of this syndrome and in patients with a history of cardiac arrhythmias or Torsade de Pointes

Sponsors & Collaborators

• University of Calgary: lead
• Hotchkiss Brain Institute, University of Calgary: collaborator

Study Sites (1)

South Health Campus

Calgary, Alberta, T3M 1M4, Canada

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Pimozide; Lactose

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Disaccharides; Oligosaccharides; Polysaccharides; Carbohydrates; Sugars

Study Officials

• Lawrence Korngut, MD, FRCPC

  University of Calgary and Alberta Health Services

  PRINCIPAL INVESTIGATOR

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: Director, Calgary ALS and Motor Neuron Disease Clinic

Study Record Dates

• First Submitted: April 21, 2015
• First Posted: June 4, 2015
• Study Start: April 1, 2015
• Primary Completion: August 1, 2016
• Study Completion: December 1, 2021
• Last Updated: October 26, 2016

Record last verified: 2016-10

Locations

CA (1)