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


University of Calgary

Status and phase

Phase 2


Amyotrophic Lateral Sclerosis (ALS)


Drug: Pimozide 4 mg per day
Drug: Placebo (Lactose tablet)
Drug: Pimozide 2 mg per day

Study type


Funder types




Details and patient eligibility


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.

Full description

This clinical trial has two components: an acute therapy component consisting of a Phase II placebo-controlled, double-blinded, randomized-controlled pilot study of pimozide for the treatment of ALS; and a second component featuring a longitudinal follow-up study on ALS progression and outcomes. This clinical trial is registry-based including subject recruitment facilitated by the Canadian Neuromuscular Disease Registry (CNDR; National Principal Investigator: L. Korngut), and longitudinal follow-up data collection will occur during the second component of this clinical trial through the CNDR. The acute therapy study duration for each subject is around 11 weeks. The follow up study duration through the CNDR is up to 5 years. Number of study participants:25 Randomization: Subjects will be block randomized with a block size of five subjects. Within each block one subject will be randomly assigned to placebo with the remaining four subjects randomized to the treatment groups. Study physicians will be blinded to patient randomization status. Randomization will occur with a 4:1 ratio of study drug (20 subjects) to placebo (5 subjects). After administration of maximum dose for 45-50 days, subjects will taper the allocated treatment or placebo. Randomization will occur via permuted block randomization and study personnel will be blinded to the randomization at all times allowing full concealment.


25 estimated patients




18+ years old


No Healthy Volunteers

Inclusion criteria

  • 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).

Exclusion criteria

  • 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
  • Presence of acquired long QT interval, such as associated with concomitant use of drugs known to prolong the QT interval
  • Presence of hypokalemia or hypomagnesemia
  • Presence of clinically significant bradycardia (heart rate < 50 beats per minute)
  • The concomitant use of CYP 3A4-inhibiting drugs such as azole antimycotics, antiviral protease inhibitors, macrolide antibiotics and nefazodone
  • The concomitant use of CYP 2D6-inhibiting drugs such as quinidine is also contraindicated
  • Concomitant use of serotonin reuptake inhibitors, such as, sertraline, paroxetine, citalopram and escitalopram
  • Severe dysphagia with risk of aspiration
  • Has taken any compound under current or known future study as a potential therapy for ALS less than 30 days prior to dosing OR history of exposure to stem cell therapy for treatment of ALS at any time

Trial design

Primary purpose




Interventional model

Parallel Assignment


Quadruple Blind

25 participants in 3 patient groups, including a placebo group

Group 1 Pimozide (2mg per day)
Experimental group
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 group
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 group
Placebo tablets will be utilized and administered in an identical manner for subjects in Group 3
Drug: Placebo (Lactose tablet)

Trial contacts and locations



Data sourced from clinicaltrials.gov

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