Amyotrophic Lateral Sclerosis (ALS) Clinical Trial
Official title:
A Registry-Based Randomized-Controlled, Double-Blinded Clinical Trial of Pimozide in Patients With Neuromuscular Junction Transmission Dysfunction Due to Amyotrophic Lateral Sclerosis
Verified date | October 2016 |
Source | University of Calgary |
Contact | n/a |
Is FDA regulated | No |
Health authority | Canada: Health Canada |
Study type | Interventional |
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.
Status | Active, not recruiting |
Enrollment | 25 |
Est. completion date | December 2021 |
Est. primary completion date | August 2016 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years and older |
Eligibility |
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 |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
Canada | South Health Campus | Calgary | Alberta |
Lead Sponsor | Collaborator |
---|---|
University of Calgary | Hotchkiss Brain Institute, University of Calgary |
Canada,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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) | No |
Primary | 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) | No |
Primary | 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) | No |
Secondary | Adverse Effects | Adverse event review will be conducted at study visits. Adverse events will be reported to the un-blinded study observer. | Day 12, visit 3 (day 23), visit 4 (day 36), visit 5 (day 51), and visit 6 (day 65). | Yes |
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