Multiple SclerosisPhase 4NCT01964547
A Randomized Study of Sativex on Cognitive Function and Mood: Multiple Sclerosis Patients
A Phase 4 study testing Sativex in people with Multiple Sclerosis and Spasticity, run by Jazz Pharmaceuticals at 1 site in Czechia.
Trial summary
A study to compare the change in cognitive performance and psychological status of patients with spasticity due to Multiple Sclerosis when treated with Sativex or placebo, added to existing anti-spasticity therapy over a period of 48 weeks. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Sclerosis, Spasticity
- What is being tested?
- Sativex
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 121 participants
- Where
- 1 siteCzechia
- Study dates
- Jan 2012to May 2013
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Patient is willing and able to give informed consent for participation in the study.
- Patient is aged 18 years or above.
- Diagnosed with any disease sub-type of multiple sclerosis.
- Diagnosed with symptomatic spasticity due to multiple sclerosis.
- Patient has at least moderate spasticity in the opinion of the investigator.
- Patient fulfils at least one of the two criteria below. Subject must be either:
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- Currently established on a regular dose of anti-spasticity therapy, or
- Previously tried and failed anti-spasticity therapy.
- Stable medication regimen for at least four weeks prior to study entry, for all medications which may have an effect on spasticity and/or cognition.
- If the patient is taking disease modifying medication this must be at a stable dose for three months prior to the initial visit.
- Willing and able to comply with all study requirements.
- Willing for his or her name to be notified to the responsible authorities for participation in this study, as applicable.
- Willing to allow his or her primary care practitioner and consultant, if appropriate, to be notified of participation in the study.
Who cannot join
- Any history or immediate family of schizophrenia, other psychotic illness, severe personality disorder or other significant psychiatric disorder other than depression associated with their underlying condition.
- Any concomitant disease or disorder (such as poorly controlled epilepsy or seizures) that may influence the patient's level of cognition or mood.
- Currently using or has used cannabis or cannabinoid-based medications within 30 days of study entry and unwilling to abstain for the duration of the study.
- Any known or suspected history of a diagnosed dependence disorder, current heavy alcohol consumption (more than 60g of pure alcohol per day for men, and more than 40g of pure alcohol per day for women), current use of an illicit drug or current non-prescribed use of any prescription drug.
- Any known or suspected hypersensitivity to cannabinoids or any of the excipients of the investigational medicinal products.
- Female patients of child bearing potential and male subjects whose partner is of child bearing potential, unless willing to ensure that they or their partner use effective contraception during the study and for three months thereafter.
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- Female patient who is pregnant, lactating or planning pregnancy during the course of the study and for three months thereafter.
- Patients who have received an investigational medicinal product within the 12 weeks prior to the initial visit.
- Any other significant disease or disorder which, in the opinion of the investigator, may either put the patient at risk because of participation in the study may influence the result of the study, or the patient's ability to participate in the study.
- Following a physical examination, the patient has any abnormalities that, in the opinion of the investigator would prevent the patient from safe participation in the study.
- Previously randomised to this study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Multicentre, Double-blind, Randomised, Parallel Group, Placebo-controlled Study of the Effect of Long-term Treatment With Sativex on Cognitive Function and Mood of Patients With Spasticity Due to Multiple Sclerosis
A study to compare the change in cognitive performance and psychological status of patients with spasticity due to Multiple Sclerosis when treated with Sativex or placebo, added to existing anti-spasticity therapy over a period of 48 weeks. Secondary objectives were to evaluate the effect of Sativex on mood and spasticity and to assess the safety and tolerability of Sativex.
Read the detailed description
Eligible patients entered this 50 week multicenter, double-blind, randomised, placebo-controlled, parallel group study which evaluated the effect of Sativex on cognitive performance. At each scheduled clinic visit, patients were assessed for cognitive performance, mood, severity of spasticity, use of investigational medicinal products and number of visits to a healthcare professional. Primary efficacy comparisons were made between scores recorded during baseline and scores recorded at the end of treatment.
- Conditions
- Multiple Sclerosis, Spasticity
- Being tested
- Sativex, Placebo
- Keywords
- Cognition, Mood
- Medical subject headings
- Multiple Sclerosis, Muscle Spasticity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SativexDrug
Also called Nabiximols, GWP42001, THC/CBD spray
Patients self-administered their allocated randomized treatment on an outpatient basis, up to a maximum of 12 sprays to the oral mucosa per day (following an initial titration period).
PlaceboDrug
Also called Placebo control
Patients self-administered their allocated randomized treatment on an outpatient basis, up to a maximum of 12 sprays to the oral mucosa per day (following an initial titration period).
| Study group | Role | What they receive |
|---|---|---|
| Sativex | Active comparator | Contains delta-9-tetrahydrocannabinol (THC), 27 mg/mL:cannabidiol (CBD), 25 mg/mL, in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavouring. Each actuation delivers THC 2.7 mg and CBD 2.5 mg.
Dose: 100 µL oromucosal spray to be administered up to a maximum of 12 sprays per day. There was an initial dose-titration period during which patients gradually increased their dose of study drug according to individual response and tolerability. Receives: Drug: Sativex |
| Placebo | Placebo comparator | Oromucosal spray, containing ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavouring and colourings FD\&C Yellow No.5 (E102 tartrazine) (0.0260%), FD\&C Yellow No.6 (E110 sunset yellow) (0.0038%), FD\&C Red No. 40 (E129 Allura red AC) (0.00330%) and FD\&C Blue No.1 (E133 Brilliant blue FCF) (0.00058%). Dose: 100 µL oromucosal spray to be administered up to a maximum of 12 sprays per day. There was an initial dose-titration period during which patients gradually increased their dose of study drug according to individual response and tolerability. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline to the End of Treatment in Paced Auditory Serial Addition Test (PASAT) Total Score.
The PASAT is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability. Stimulus presentation rates were adapted for use with multiple sclerosis patients. The PASAT is presented on audio compact disk to control the rate of stimulus presentation. Single digits are presented either every 3 seconds (PASAT 1) or every 2 seconds (PASAT 2), and the patient must add each new digit to the one immediately prior to it. The test score is the sum of the total number of correct sums given (out of 60 possible) in each trial. An increase in score indicates an improvement in condition.
Measured: 0-48 weeks
Secondary outcomes (9)
Change From Baseline to the End of Treatment in Beck Depression Inventory-II (BDI-II) Total Score.
The BDI-II is a multiple choice self-reported inventory that is one of the most widely used instruments for measuring the severity of depression. There are 21 questions or items, each having four possible responses. Each response is assigned a score ranging from zero to three, indicating the severity of the symptom. Items 1 to 13 assess symptoms that are psychological in nature, while items 14 to 21 assess symptoms that are more physical. The sum of all BDI-II item scores indicates the severity of depression. For patients eligible for this study, a score of 21 or over represents depression. The BDI-II can distinguish between different subtypes of depressive disorders, such as major depression and dysthymia. A reduction in score indicates an improvement in condition.
Measured: 0-48 weeks
Subject Global Impression of Change (SGIC) in the Severity of Their Spasticity at the End of Treatment.
Patients were asked the following question, to be rated on a seven-point scale:
"Please assess the change in your spasticity since immediately before receiving the first dose of study treatment (Visit 1) using the scale below".
The markers were: 'Very much worse', 'Much worse', 'Minimally worse', 'No change', 'Minimally better', 'Much better' or 'Very much better'.
The number of patients for each of the markers is presented at the final study visit.
Measured: 0-48 weeks
Caregiver's Global Impression of Change (CGIC) in the Severity of the Patient's Spasticity at the End of Treatment.
Caregivers were asked the following question to be rated on a seven-point scale:
"How has the subject's spasticity changed since Visit 1?" The markers were: Very much worse, Much worse, Minimally worse, No change, Minimally better, Much better, Very much better.
The number of patients for each of the markers is presented at the final study visit.
Measured: 0-48 weeks
Physician's Global Impression of Change (PGIC) in the Severity of the Patient's Spasticity at the End of Treatment.
Physicians were asked the following question to be rated on a seven-point scale:
"How has the subject's spasticity changed since Visit 1?" The markers were: Very much worse, Much worse, Minimally worse, No change, Minimally better, Much better, Very much better.
The number of patients for each of the markers is presented at the final study visit.
Measured: 0-48 weeks
Change From Baseline to End of Treatment in Modified Ashworth Scale Total Score.
All 20 muscle groups were assessed for spasticity (using a 0-5 scale): 0= 'no increase in muscle tone' to 5= 'affected part(s) rigid in flexion or extension'. The score for all 20 muscle groups were added to give a total score out of 100. A decrease in score indicates an improvement in condition.
Measured: 0-48 weeks
Change From Baseline to End of Treatment in Number of Visits to a Healthcare Professional.
At baseline, patients were asked how many times they had visited a healthcare professional in the previous 12 weeks. At subsequent visits, patients were asked how many times they had visited a healthcare professional since their last study visit. The change from baseline to the end of treatment is presented. A decrease in number indicates an improvement in condition.
Measured: 0-48 weeks
The Number of Patients With a Treatment-emergent Flag Using the Columbia-Suicide Severity Rating Scale (C-SSRS) During the Course of the Study.
Patients were scored at each clinic visit for the following outcomes using the C-SSRS: suicidal ideation, suicidal behaviour, suicidality (including complete suicidality). Possible flags were as follows: "Wish to be Dead", "Non-specific Active Suicidal Thoughts", "Active Suicidal Ideation Without Intent", "Active Suicidal Ideation With Intent, No Plan", "Active Suicidal Ideation With Intent and Plan". The number of patients with a treatment-emergent flag is presented.
Measured: 0-48 weeks
Change From Baseline to End of Treatment in Timed 10-meter Walk Times.
Only those patients for whom it was appropriate (i.e. ambulatory patients) were timed for how long it took to walk 10 metres. If a patient started the 10-meter walk but was unable to complete it, an estimated time for completion was calculated based on the available data. A negative difference from baseline indicates an improvement in condition.
Measured: 0-48 weeks
Incidence of Adverse Events as a Measure of Patient Safety.
The number of subjects who experienced an adverse event during the course of the study is presented.
Measured: 0-50 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2013 (estimated)
- Study startJan 2012
- Primary completionMay 2013
- Study completionMay 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Jazz PharmaceuticalsThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 121 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jazz Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01964547
- Sponsor's protocol ID
- GWMS1137
- Status last verified
- Dec 2022
- First submitted
- 15 Oct 2013
- Last updated
- 12 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Abstracts of ECTRIMS (Congress of the European Committee for Treatment and Research in Multiple Sclerosis) 2013. October 2-5, 2013. Copenhagen, Denmark. Mult Scler. 2013 Oct;19(11 Suppl):8-597. No abstract available.
PubMed 24151639Bosnjak Kuharic D, Markovic D, Brkovic T, Jeric Kegalj M, Rubic Z, Vuica Vukasovic A, Jeroncic A, Puljak L. Cannabinoids for the treatment of dementia. Cochrane Database Syst Rev. 2021 Sep 17;9(9):CD012820. doi: 10.1002/14651858.CD012820.pub2.
PubMed 34532852
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicentre, Double-blind, Randomised, Parallel Group, Placebo-controlled Study of the Effect of Long-term Treatment With Sativex on Cognitive Function and Mood of Patients With Spasticity Due to Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT01964547
- Acronym / sponsor ID
- GWMS1137
- Conditions
- Multiple Sclerosis, Spasticity
- Keywords
- Cognition, Mood
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 121 participants (actual)
- Lead sponsor
- Jazz PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jan 2012
- Primary completion
- May 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 17 Oct 2013 (estimated)
- Results
- Posted 2 May 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A study to compare the change in cognitive performance and psychological status of patients with spasticity due to Multiple Sclerosis when treated with Sativex or placebo, added to existing anti-spasticity therapy over a period of 48 weeks. Secondary objectives were to evaluate the effect of Sativex on mood and spasticity and to assess the safety and tolerability of Sativex.
Detailed description
Eligible patients entered this 50 week multicenter, double-blind, randomised, placebo-controlled, parallel group study which evaluated the effect of Sativex on cognitive performance. At each scheduled clinic visit, patients were assessed for cognitive performance, mood, severity of spasticity, use of investigational medicinal products and number of visits to a healthcare professional. Primary efficacy comparisons were made between scores recorded during baseline and scores recorded at the end of treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sativex | Active comparator | Drug: SativexContains delta-9-tetrahydrocannabinol (THC), 27 mg/mL:cannabidiol (CBD), 25 mg/mL, in ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavouring. Each actuation delivers THC 2.7 mg and CBD 2.5 mg. Dose: 100 µL oromucosal spray to be administered up to a maximum of 12 sprays per day. There was an initial dose-titration period during which patients gradually increased their dose of study drug according to individual response and tolerability. |
| Placebo | Placebo comparator | Drug: PlaceboOromucosal spray, containing ethanol:propylene glycol (50:50) excipients, with peppermint oil (0.05%) flavouring and colourings FD\&C Yellow No.5 (E102 tartrazine) (0.0260%), FD\&C Yellow No.6 (E110 sunset yellow) (0.0038%), FD\&C Red No. 40 (E129 Allura red AC) (0.00330%) and FD\&C Blue No.1 (E133 Brilliant blue FCF) (0.00058%). Dose: 100 µL oromucosal spray to be administered up to a maximum of 12 sprays per day. There was an initial dose-titration period during which patients gradually increased their dose of study drug according to individual response and tolerability. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Patient is willing and able to give informed consent for participation in the study.
- Patient is aged 18 years or above.
- Diagnosed with any disease sub-type of multiple sclerosis.
- Diagnosed with symptomatic spasticity due to multiple sclerosis.
- Patient has at least moderate spasticity in the opinion of the investigator.
Key exclusion criteria (11 listed)
- Any history or immediate family of schizophrenia, other psychotic illness, severe personality disorder or other significant psychiatric disorder other than depression associated with their underlying condition.
- Any concomitant disease or disorder (such as poorly controlled epilepsy or seizures) that may influence the patient's level of cognition or mood.
- Currently using or has used cannabis or cannabinoid-based medications within 30 days of study entry and unwilling to abstain for the duration of the study.
- Any known or suspected history of a diagnosed dependence disorder, current heavy alcohol consumption (more than 60g of pure alcohol per day for men, and more than 40g of pure alcohol per day for women), current use of an illicit drug or current non-prescribed use of any prescription drug.
- Any known or suspected hypersensitivity to cannabinoids or any of the excipients of the investigational medicinal products.
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 |
|---|---|---|
| SativexAlso: Nabiximols, GWP42001, THC/CBD sprayPatients self-administered their allocated randomized treatment on an outpatient basis, up to a maximum of 12 sprays to the oral mucosa per day (following an initial titration period). | Drug | Sativex |
| PlaceboAlso: Placebo controlPatients self-administered their allocated randomized treatment on an outpatient basis, up to a maximum of 12 sprays to the oral mucosa per day (following an initial titration period). | Drug | Placebo |
Primary outcome
Change From Baseline to the End of Treatment in Paced Auditory Serial Addition Test (PASAT) Total Score.
Time frame: 0-48 weeks
The PASAT is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability. Stimulus presentation rates were adapted for use with multiple sclerosis patients. The PASAT is presented on audio compact disk to control the rate of stimulus presentation. Single digits are presented either every 3 seconds (PASAT 1) or every 2 seconds (PASAT 2), and the patient must add each new digit to the one immediately prior to it. The test score is the sum of the total number of correct sums given (out of 60 possible) in each trial. An increase in score indicates an improvement in condition.
9 secondary outcomes
Change From Baseline to the End of Treatment in Beck Depression Inventory-II (BDI-II) Total Score.
Time frame: 0-48 weeks
Subject Global Impression of Change (SGIC) in the Severity of Their Spasticity at the End of Treatment.
Time frame: 0-48 weeks
Caregiver's Global Impression of Change (CGIC) in the Severity of the Patient's Spasticity at the End of Treatment.
Time frame: 0-48 weeks
Physician's Global Impression of Change (PGIC) in the Severity of the Patient's Spasticity at the End of Treatment.
Time frame: 0-48 weeks
Change From Baseline to End of Treatment in Modified Ashworth Scale Total Score.
Time frame: 0-48 weeks
Change From Baseline to End of Treatment in Number of Visits to a Healthcare Professional.
Time frame: 0-48 weeks
The Number of Patients With a Treatment-emergent Flag Using the Columbia-Suicide Severity Rating Scale (C-SSRS) During the Course of the Study.
Time frame: 0-48 weeks
Change From Baseline to End of Treatment in Timed 10-meter Walk Times.
Time frame: 0-48 weeks
Incidence of Adverse Events as a Measure of Patient Safety.
Time frame: 0-50 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 24151639Abstracts of ECTRIMS (Congress of the European Committee for Treatment and Research in Multiple Sclerosis) 2013. October 2-5, 2013. Copenhagen, Denmark. Mult Scler. 2013 Oct;19(11 Suppl):8-597. No abstract available.
- Derived from this study: PubMed 34532852Bosnjak Kuharic D, Markovic D, Brkovic T, Jeric Kegalj M, Rubic Z, Vuica Vukasovic A, Jeroncic A, Puljak L. Cannabinoids for the treatment of dementia. Cochrane Database Syst Rev. 2021 Sep 17;9(9):CD012820. doi: 10.1002/14651858.CD012820.pub2.
- P1206: Abstract of study data presented at ECTRIMS 2013Link provided by the sponsor.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Sativex in people with Multiple Sclerosis and Spasticity, run by Jazz Pharmaceuticals at 1 site in Czechia.
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 13 inclusion and 11 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: finished, as of the sponsor's last update on 12 Jan 2023. 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 Czechia. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 May 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change From Baseline to the End of Treatment in Paced Auditory Serial Addition Test (PASAT) Total Score. (time frame: 0-48 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01964547, which also lists 2 linked publications.
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 12 Jan 2023.