Clinical trial NCT00678795: A Parallel Group Study to Compare Sativex® With Placebo in the Treatment of Detrusor Overactivity in Patients With Multiple Sclerosis
Official title: A Double Blind, Randomised, Placebo Controlled, Parallel Group Study of Cannabis Based Medicine (CBM) Extract, in Patients Suffering Detrusor Overactivity Associated With Multiple Sclerosis.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Detrusor Overactivity
Multiple Sclerosis
Keywords: Detrusor overactivity
Multiple Sclerosis
Lead sponsor: Jazz Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2008-05-16
Enrollment: 135
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: The purpose of this study is to evaluate the efficacy of Sativex® compared with placebo in reducing the daily number of episodes on incontinence.

Detailed description: This is a ten week, multicentre, double blind, randomised, placebo controlled parallel group study to evaluate the efficacy of Sativex® on urge incontinence associated with neurogenic unstable bladder. Multiple sclerosis patients with incontinence symptoms are screened to determine eligibility and complete a two-week baseline period. They then return for a further eligibility check, randomisation and initial dosing. Subjects titrate and self-medicate with study medication between study visits at weeks two and five. They will also complete efficacy assessments in their diary-books and at visits.

Eligibility criteria: Inclusion Criteria:

* Willing and able to give informed consent.
* Male or female, aged 18 years or over.
* Diagnosed with MS and with detrusor overactivity not wholly relieved by current therapy.
* At least three incontinence episodes within five consecutive days during the baseline period
* Stable dose of anticholinergic medication for at least 14 days leading to study entry.
* Agreement, if female and of child bearing potential or if male with a partner of child bearing potential, to ensure that effective contraception is used during the study and for three months thereafter.
* Has not used cannabinoids (including cannabis, Marinol® or nabilone) for at least seven days before Visit 1 and willing to abstain from any use of cannabinoids during the study.
* Agreement for the UK Home Office, their general practitioner, and their consultant if appropriate, to be notified of their participation in the study.

Exclusion Criteria:

* A symptomatic UTI or any cause of detrusor overactivity other than neurogenic causes due to MS.
* Using ISC.
* A history of schizophrenia, other psychotic illness, severe personality disorder or other significant psychiatric disorder other than depression associated with their underlying condition.
* A history of alcohol or substance abuse.
* A severe cardiovascular disorder, such as ischaemic heart disease, arrhythmias (other than well controlled atrial fibrillation), poorly controlled hypertension or severe heart failure.
* A history of epilepsy.
* If female, are pregnant of lactating, or are planning a pregnancy to occur during the course of the study.
* Significant renal or hepatic impairment.
* Elective surgery or other procedures requiring general anesthesia scheduled to occur during the study.
* Terminal illness or any other significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study or influence the result of the study, or the subjects ability to participate in the study.
* Regular levodopa (Sinement®, Sinement Plus®, Levodopa, L-dopa, Madopar®, Benserazide) within the seven days leading up to study entry.
* Receiving and unwilling to stop fentanyl for the duration of the study.
* Known or suspected hypersensitivity to cannabinoids or any of the excipients of the study medications.
* Intention to travel internationally or to donate blood during the study.
* Participation in another research study in the 12 weeks leading up to study entry.
* Previous randomization in to this study

Primary outcomes:
measure: Change From Baseline in the Mean Daily Number of Incontinence Episodes at the End of Treatment
timeFrame: 0 - 10 weeks
Secondary outcomes:
measure: Change From Baseline in the Mean Daily Episodes of Urgency at the End of Treatment
timeFrame: Daily diary entries throughout 10 week study period
measure: Change From Baseline in the Mean Daily Episodes of Nocturia at the End of Treatment
timeFrame: 0 - 10 weeks
measure: Change From Baseline in the Mean Daily Number of Incontinence Pads Used at the End of Treatment
timeFrame: 0 - 10 weeks
measure: Change From Baseline in Mean Total Incontinence Quality of Life (I-QOL) Questionnaire Score at the End of Treatment (Completion or Withdrawal)
timeFrame: 0 - 10 weeks
measure: Change From Baseline in Mean Overall Bladder Condition 0-10 Numerical Rating Scale Score at the End of Treatment
timeFrame: 0 - 10 weeks
measure: Patient's Global Impression of Change
timeFrame: 0 - 10 weeks
measure: Change From Baseline in the Mean Number of Daily Voids at the End of Treatment
timeFrame: 0 - 10 weeks
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: Division of Clinical Neurology, Queen's Medical Centre
state: Notts
Study officials:
affiliation: Division of Clinical Neurology, Queen's Medical Centre
name: Cris Constantinescu, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kavia RB, De Ridder D, Constantinescu CS, Stott CG, Fowler CJ. Randomized controlled trial of Sativex to treat detrusor overactivity in multiple sclerosis. Mult Scler. 2010 Nov;16(11):1349-59. doi: 10.1177/1352458510378020. Epub 2010 Sep 9.