Amyotrophic Lateral Sclerosis (ALS)Phase 2NCT02463825
A Registry-Based Clinical Trial of Pimozide in Patients With Neuromuscular Junction Transmission Dysfunction Due to ALS
A Phase 2 study testing Pimozide 2 mg per day and Pimozide 4 mg per day in people with Amyotrophic Lateral Sclerosis (ALS), run by University of Calgary at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Amyotrophic Lateral Sclerosis (ALS)
- What is being tested?
- Pimozide 2 mg per day and Pimozide 4 mg per day
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 1 siteCanada
- Study dates
- Apr 2015to Dec 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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
Show all 23Show fewer
- 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 locations and contacts
1 site in 1 country.
About this study
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
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.
Read the detailed 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.
- Conditions
- Amyotrophic Lateral Sclerosis (ALS)
- Being tested
- Pimozide 2 mg per day, Pimozide 4 mg per day, Placebo (Lactose tablet)
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pimozide 2 mg per dayDrug
Pimozide 4 mg per dayDrug
Placebo (Lactose tablet)Drug
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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). Receives: 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 Receives: Drug: Placebo (Lactose tablet) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 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.
Measured: 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
Adverse event review will be conducted at study visits. Adverse events will be reported to the un-blinded study observer.
Measured: Day 12, visit 3 (day 23), visit 4 (day 36), visit 5 (day 51), and visit 6 (day 65).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2015 (estimated)
- Study startApr 2015
- Primary completionAug 2016
- Study completionDec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Amyotrophic Lateral Sclerosis (ALS)Studies of the same condition, open and under way.
- More trials run by University of CalgaryThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Calgary
- Sponsor type
- University, hospital or other
- Collaborators
- Hotchkiss Brain Institute, University of Calgary
- Responsible party
- Principal investigator, DR. LAWRENCE KORNGUT, University of Calgary
- Investigators
- Lawrence Korngut, MD, FRCPC, Principal investigator, University of Calgary and Alberta Health Services
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02463825
- Sponsor's protocol ID
- REB14-0617
- Status last verified
- Oct 2016
- First submitted
- 21 Apr 2015
- Last updated
- 26 Oct 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02463825
- Acronym / sponsor ID
- REB14-0617
- Conditions
- Amyotrophic Lateral Sclerosis (ALS)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- University of CalgaryUniversity, hospital or other
- Collaborators
- Hotchkiss Brain Institute, University of Calgary
- Study start
- Apr 2015
- Primary completion
- Aug 2016 (actual)
- Study completion
- Dec 2021 (estimated)
- First posted
- 4 Jun 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1 Pimozide (2mg per day) | Experimental | Drug: Pimozide 2 mg per dayPimozide 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. |
| Group 2 Pimozide (4mg per day) | Experimental | Drug: Pimozide 4 mg per dayPimozide 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). |
| Group 3 Placebo (Lactose tablet) | Placebo comparator | Drug: Placebo (Lactose tablet)Placebo tablets will be utilized and administered in an identical manner for subjects in Group 3 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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).
Key exclusion criteria (23 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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) |
Primary outcome
ALS Functional Rating Scale-Revised (ALSFRS-R)
Time frame: Change from randomization in ALSRSR-R at visit 5(day 51) and change from randomization in ALSFRS-R at visit 6 (day 65)
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
Slow Vital Capacity (SVC)
Time frame: 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)
SVC will be measured using a spirometer.
Decremental responses on repetitive nerve stimulation (DRRNS)
Time frame: 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)
Using Caldwell Electromyographic System, perform repetitive nerve stimulation studies and estimates of amplitude of decremental responses.
1 secondary outcome
Adverse Effects
Time frame: Day 12, visit 3 (day 23), visit 4 (day 36), visit 5 (day 51), and visit 6 (day 65).
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lawrence Korngut, MD, FRCPC principal investigator
University of Calgary and Alberta Health Services
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pimozide 2 mg per day and Pimozide 4 mg per day in people with Amyotrophic Lateral Sclerosis (ALS), run by University of Calgary at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 26 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ALS Functional Rating Scale-Revised (ALSFRS-R) (time frame: Change from randomization in ALSRSR-R at visit 5(day 51) and change from randomization in ALSFRS-R at visit 6 (day 65)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2016.