The CanISleepinMS Study: Effect of cannabidiol (CBD) on sleep quality in patients with multiple sclerosis, a series of 15 randomised, placebo-controlled N-of-1 trials

Phase 2

• Conditions: Slaapkwaliteit; Sleep quality

• Registration Number: NL-OMON56335
• Lead Sponsor: Wageningen Universiteit

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Pending
• Sex: Not specified
• Target Recruitment: 15

Inclusion Criteria

• A diagnosis of MS confirmed by a neurologist, based on the revised 2010 or
2017 McDonalds criteria • Relapsing-remitting or primary or secondary
progressive MS • Expanded Disability Status Scale (EDSS) score < 7.5 • No
relapse for at least 6 months before the screening visit • No changes in
immunomodulating therapy stable for at least 3 months before the screening
visit; no changes in use of other medications used for chronic conditions for
at least 6 weeks before the screening visit (e.g. anti-depressant drugs,
antidiabetics) • Age minimally 18 years at the time of screening • Body Mass
Index (BMI) < 35.0 kg/m2 at the moment of screening. • Elevated levels of
transaminases (ALAT, ASAT) until twice the Upper Limit of Normal (2x ULN) are
allowed, as elevation of these levels is a common finding in MS patients. • No
plans to (be involved in) getting pregnant during the trial. • No breast
feeding during the trial • A complaint of chronic impairment of sleep quality,
leading to a diagnosis of insomnia by an MS neurologist and an experienced
somnologist. In this context, insomnia is defined as difficulties initiating
and/or maintaining sleep or too early awakenings, despite adequate opportunity
and circumstances for sleep, resulting in some form of daytime impairment.
Causes include psychophysiological insomnia, insomnia due to mental disorders
like depression, and insomnia secondary to other MS-related symptoms like
spasticity, pain or nocturnal voidings. Diagnosis will be based on fulfilment
of the ICDS-3 criteria of insomnia and an ISI score of minimally 15 (threshold
for clinical insomnia). • Continuation of pharmacological treatments will be at
the discretion of the study physicians. • Willing and able to refrain from new,
sleep-facilitating pharmacological treatments until the end of the treatment
phase of the study • Willing and able not to use any other cannabis product
until completion of the study • Willing and able not to use any supplement that
could promote sleep (e.g. L-tryptophan, valerian, melatonin) during the
treatment phase of the study. • Continuation of non-pharmacological treatments
will be at the discretion of the study physicians. • Willing and able to
refrain from new, sleep-facilitating non-pharmaceutical interventions until the
end of the treatment phase of the study. Lifestyle should be kept as stable as
possible. • Willing and able to give informed consent • Willing and able to
fill in a daily digital diary during the treatment phase, to send this to the
study nurse or research assistant once a week, and to be contacted by the
research assistant minimally twice a week during the treatment phase of the
study • Willing and able to use the Neurokeys app (thus mobile phone) daily •
Willing to have blood sampled at the screening visit and have another two blood
draws during the treatment phase of the study • Willing and able not to drive a
car or operate machinery within 8 hours after intake of the investigational
product until the end of the treatment phase of the study • Willing and able
not to do evening/night shift work and not to cross time zones until the
completion of the study • Willing and able to refrain from excessive use of
excessive use of caffeine (> 1 cup of coffee or 1 serving of energy drink) and
alcohol (> 1 serving) in the ev

Exclusion Criteria

• Circadian rhythm sleep-wake disorders, sleep related breathing disorders
(such as moderate to severe obstructive sleep apnea, central breathing
disorders during sleep, or sleep-related stridor that require prompt specific
treatment), current delayed sleep phase syndrome where wake up time is
regularly later than 8.00 a.m., or a sleep problem fulfilling the ICSD3
criteria of parasomnias • Good response to initial treatment for the assessed
sleep disorder • Use of a benzodiazepine or other sleep medication, unless the
patient has tapered off the sleep medication before the moment of inclusion •
Liver disease or blood levels of transaminases (ALAT, ASAT) above 3x ULN, as
long term administration of high doses of CBD may affect (although reversible)
liver function • History of severe psychiatric comorbidity • Increased risk of
suicidal thoughts or behaviour • History of drug or alcohol abuse • Known or
suspected hypersensitivity to cannabinoids or to excipients of the formulation
of the investigational product - almond oil • History of use with CBD oil
prepared by pharmacy Clinical Cannabis Care • Structural or recreational use of
a cannabinoid product < 2 months before screening • Whether the use of any of
the following medications is a reason for exclusion will be at the discretion
of the study physicians and delivery pharmacist. o drugs with risk of liver
injury; the decision of exclusion will be made in consultation with the MS
neurologists and the pharmacist that provides the CBD product. o drugs with
risk of interaction with CBD. Data on the potential drug-CBD interactions below
are based on mechanistic and clinical studies: • Drugs of which their
biotransformation is primarily dependent on the cytochrome P450 enzymes CYP2C19
and CYP3A • Drugs that are inducers or inhibitors of enzymes of which CBD is a
substrate: CYP2C19, CYP3A4.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Insomnia Severity Index (ISI) score</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Diary measurements (sleep-related outcomes: number of awakenings (NA), Sleep<br /><br>Onset Latency (SOL), Sleep Efficiency (SE), Wake time After Sleep Onset (WASO),<br /><br>Total Sleep Time (TST); non-sleep outcomes: changes in number of nocturnal<br /><br>voidings, number, type, and severity of adverse events (AEs);<br /><br>Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS), Checklist<br /><br>Individual Strength Fatigue-subschaal (CIS-F);<br /><br>Keystroke features of the Neurocast® App, a 24/7 digital measure of fatigue,<br /><br>rest and activity patterns, and daily functioning based on dynamics of keyboard<br /><br>key strokes on personal smartphones; furthermore answers on daily pop-up<br /><br>questions for Numeric Rating Scale (NRS) scores for pain, spasms, and fatigue;</p><br>