This study has been transitioned to CTIS with ID 2024-518280-35-00 check the CTIS register for the current data. To investigate the effect of CBD on MS patients with impaired sleep quality.
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Slaapkwaliteit
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Insomnia Severity Index (ISI) score
Secondary outcome
Diary measurements (sleep-related outcomes: number of awakenings (NA), Sleep
Onset Latency (SOL), Sleep Efficiency (SE), Wake time After Sleep Onset (WASO),
Total Sleep Time (TST); non-sleep outcomes: changes in number of nocturnal
voidings, number, type, and severity of adverse events (AEs);
Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS), Checklist
Individual Strength Fatigue-subschaal (CIS-F);
Keystroke features of the Neurocast® App, a 24/7 digital measure of fatigue,
rest and activity patterns, and daily functioning based on dynamics of keyboard
key strokes on personal smartphones; furthermore answers on daily pop-up
questions for Numeric Rating Scale (NRS) scores for pain, spasms, and fatigue;
Background summary
The high prevalence of impaired sleep quality in multiple sclerosis (MS) has an
impact on the patient*s quality of life and disease burden. Therapeutic options
include cognitive behavioural therapy and the use of hypnotics. The former is
considered a cornerstone but is not widely available and is
labour-intensive.The use of hypnotics can be problematic as their long-term use
can be associated with tolerance, dependence and side effects.Data from
pre-clinical studies and reports from case-studies - albeit of varying quality
- have attracted the attention of patients and practitioners to use cannabis
products as an alternative option. A medicinal cannabis preparation, registered
as Sativex® containing tetrahydrocannabinol (THC) and cannabidiol (CBD) is
already available as additional treatment of specifically spasticity in MS.
Reports from patients, patient organisations and health care professionals,
underlined by patient surveys consistently suggest widespread use of
uncontrolled cannabis products - inevitably of varying quality - by MS
patients, with the aim of improving their sleep quality. To date, there is no
substantial evidence of cannabinoid effectiveness on human sleep quality.
Furthermore, the THC component of cannabis has psychoactive, cardiovascular,
and addictive properties.12 In contrast, the non-psychoactive CBD component has
a considerably better safety profile next to the potential to improve several
physiological conditions, including sleep.Therefore, we want to investigate the
effect of CBD on sleep quality in MS patients in the present study.
Study objective
This study has been transitioned to CTIS with ID 2024-518280-35-00 check the CTIS register for the current data.
To investigate the effect of CBD on MS patients with impaired sleep quality.
Study design
A series of 15 N-of-1 trials investigating the effects of CBD in MS patients
with chronic impairment of sleep quality. Each N-of-1 trial will consist of two
crossover studies performed in a single patient. Within a crossover, the
interventions with either CBD or placebo are randomised and double blinded.
After a run-in period of 2 weeks, there will be 4 treatment periods of 3 weeks,
separated from each other by a washout of 1 week.
Intervention
In week 1 of the treatment phase, trial participants take either a solution of
CBD (10% w/v) in almond oil for oromucosal administration at a dose of 150 mg
once daily or a placebo, 30 minutes before going to bed at night. In weeks 2
and 3 of the treatment phase, trial participants take either a solution of CBD
(10% w/v) in almond oil for oromucosal administration at a dose of 300 mg once
daily or a placebo, 30 minutes before going to bed at night.
There are 4 treatment periods of 3 weeks, separated by a wash-out period of 1
week.
Study burden and risks
With respect to patient burden the following key figures are of relevance. The
total study duration for a single participant will be 18 weeks consisting of a
run-in period of 2 weeks, 4 treatment periods of 3 weeks which are separated by
a washout period of 1 week, and a last contact moment in week 18. There will be
a first physical appointment in the Rijnstate Hospital for screening, and blood
will be taken. Halfway through the study and at the end there will be another
two physical appointments for blood sampling.
Furthermore, during the 16 week-lasting intervention phase the participant is
required to collect measurements as planned in the protocol, which will take
time and effort. First, each day a participant is required to record sleep- and
non sleep-related outcomes in a digital diary. Once a week the diary recordings
have to be sent to the research assistant. Subsequently, the participant will
be contacted by telephone by the research assistant about these recordings to
discuss and, if desired, further elaborate on the experiences and to check how
the participant is doing. In addition, the participant will be provided with
questionnaires by the study nurse weekly. The participant will also be required
to install a 24/7 digital recording app (NeurokeysR) on his/her mobile phone
which monitors keyboard key stroke patterns. Sometimes it takes some time to
get used to this keyboard . The data recorded will be extracted by the study
nurse at the end of the run-in period and after each treatment period.
Another element of patient burden is that the participant should be willing to
comply with the requirements of the study protocol, among which being willing
to take a purified CBD product or a placebo once daily, 30 minutes before going
to bed in the evening.
Risks associated with participation are minimal. CBD is considered non-toxic,
non-psychoactive, and non-addictive. Adverse effects reported in animal studies
are associated with doses far exceeding those recommended for humans. The
maximum dose foreseen in our study of 300 mg CBD once daily is also
substantially lower than the maximum dose of twice daily 10 mg/kg body weight
of an approved medicinal CBD preparation to control seizures, Epidiolex® (in an
80-kg person this corresponds to 800 mg twice daily). Of relevance would be a
risk of CBD- drug interactions to occur as CBD is known for its inhibitory
effects on some cytochrome P450 (CYP450) and UPGT-enzymes (glucuronidation)
next to serving as a substrate of CYP450 enzymes itself.A change in effectivity
of drugs respectively CBD may be the consequence. In Appendix C1 an overview is
given of medications interacting with CBD.Before final enrolment of a patient,
the potential risk of interactions will be evaluated by the study pharmacist.
This study will create more insights into the effects of CBD on sleep quality
in MS. The results This study may benefit sleep quality of the individual
participants and prevent them from experimenting with freely available cannabis
products of varying quality, which may lead to unexpected side effects because
of the high prevalence of impaired sleep quality accompanied with daytime
consequences in the MS population. Thus, this study may create more insight
into the effects of a safe CBD product on sleep quality of MS patients.
Stippeneng 4
Wageningen 6708 WE
NL
Stippeneng 4
Wageningen 6708 WE
NL
Listed location countries
Age
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 evening, 6 hours before going to bed • Willing and
able to refrain from (products of) grapefruit, Seville oranges (used in
marmalade), limes and pomelos during the treatment phase of the study. •
Willing and able to refrain from experimenting with timing and type of diet,
and beverages during the treatment phase of the study. A participant*s dietary
intake pattern should be kept as stable as possible during the treatment phase
as there are numerous dietary components other than furanocoumarins that may
influence CBD bioavailability
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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-518280-35-00 |
| EudraCT | EUCTR2022-002372-36-NL |
| CCMO | NL83212.091.22 |