A Registry-Based Randomized-Controlled, Double-Blinded Clinical Trial of Pimozide in Patients With Neuromuscular Junction Transmission Dysfunction Due to Amyotrophic Lateral Sclerosis

Study Purpose:

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.

Study Status:

Not recruiting


Amyotrophic Lateral Sclerosis (ALS)

Study Type:


Type of Intervention:


Intervention Name:

Pimozide 2 mg per day, Pimozide 4 mg per day, Placebo (Lactose tablet)



Phase 2

Study Chair(s)/Principal Investigator(s):

Lawrence Korngut, MD, FRCPC, University of Calgary and Alberta Health Services

Clinicaltrials.gov ID:


Neals Affiliated?


Coordinating Center Contact Information

University of Calgary

Calgary, United States

Full Study Summary:

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.

Study Sponsor:

University of Calgary

Participant Duration:

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.

Estimated Enrollment:


Estimated Study Start Date:

03 / 31 / 2015

Estimated Study Completion Date:

12 / 01 / 2021

Posting Last Modified Date:

10 / 26 / 2016

Date Study Added to neals.org:

06 / 04 / 2015

Minimum Age:

18 Years

Maximum Age:


Can participants use Riluzole?


Inclusion Criteria:

1. Patients classified as having clinically definite, clinically probable, or clinically probable (laboratory-supported) ALS according to the El-Escorial diagnostic criteria for ALS

2. Evidence of decremental response greater or equal to 5.0% in at least one nerve-muscle pair at the initial screening visit

3. Age 18 years or greater

4. Consent to participate in the Canadian Neuromuscular Disease Registry (CNDR) (follow-up study component only).

Exclusion Criteria:

1. Diagnosis of clinically possible or clinically suspected ALS as defined by the El-Escorial diagnostic criteria for ALS

2. 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.

3. History of Parkinson's disease

4. History of traumatic brain injury

5. History of neuroleptic malignant syndrome

6. History of hypersensitivity or serious adverse reaction(s) to a neuroleptic medication

7. History of prolonged QTc interval > 500 ms

8. History of hyponatremia < 130 mmol/L

9. History of current heparin or warfarin use

10. History of hepatic and/or renal impairment that may affect pimozide metabolism

11. History of current pregnancy or breastfeeding

12. Current antipsychotic use

13. Presence of central nervous system depression, comatose states, liver disorders, renal insufficiency, and blood dyscrasias

14. Presence of depressive disorders or Parkinson's syndrome

15. 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

16. Presence of acquired long QT interval, such as associated with concomitant use of drugs known to prolong the QT interval

17. Presence of hypokalemia or hypomagnesemia

18. Presence of clinically significant bradycardia (heart rate < 50 beats per minute)

19. The concomitant use of CYP 3A4-inhibiting drugs such as azole antimycotics, antiviral protease inhibitors, macrolide antibiotics and nefazodone

20. The concomitant use of CYP 2D6-inhibiting drugs such as quinidine is also contraindicated

21. Concomitant use of serotonin reuptake inhibitors, such as, sertraline, paroxetine, citalopram and escitalopram

22. Severe dysphagia with risk of aspiration

23. 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

South Health Campus

Calgary, Alberta T3M 1M4