Condition category
Urological and Genital Diseases
Date applied
04/04/2013
Date assigned
04/04/2013
Last edited
30/03/2017
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Nocturia is a condition that means getting up at night one or more times to pass urine. The bladder is controlled via the brain, spinal cord, and nerves. Therefore, many neurological conditions can also have an effect on bladder function. This can occur in multiple sclerosis, and this can lead to symptoms of frequent urination as well as nocturia. It is a common condition in both men and women and this can have a significant impact on quality of sleep and quality of life. The aim of this study is to investigate the effect of melatonin on nocturia in adults with progressive multiple sclerosis. In multiple sclerosis urinary symptoms are common, including nocturia. Melatonin is a naturally occurring hormone in humans which regulates the normal circadian cycles (the natural pattern of physical and behavioral processes) in each 24-hour period. Melatonin seems to help sleep and control the timing of the sleep period. It is possible that nocturia may be a sign of impaired circadian regulation. In this instance, taking melatonin as a sustained-release tablet may improve nocturia, sleep quality and quality of life in patients with multiple sclerosis.

Who can participate?
Patients aged 18 to 80 with multiple sclerosis and nocturia

What does the study involve?
Participants are asked to attend the clinic for a screening visit (Visit 1) to see if they are suitable to take part in the study. If they are suitable to take part they come back for regular visits to check their progress in the study. It is a crossover study, which means that participants are randomly allocated to receive either melatonin or placebo (dummy drug) in the first treatment period, and in the second treatment period they receive the opposite of they were given (either melatonin or placebo) in the first treatment period. The two treatment periods last 6 weeks each and are separated by a break of 1 month. The number of nocturia episodes per night are measured at the start of the study and at the end of each treatment period. After the second treatment period, participants can continue to take melatonin for 1 year. Participants are interviewed to assess the impact of nocturia on their quality of life.

What are the possible benefits and risks of participating?
Melatonin may reduce how often people with multiple sclerosis have to pass urine during the night, and therefore may reduce urinary symptoms and fatigue, and improve overall quality of life. Melatonin appears to cause very few side effects in the short term, up to 3 months, when healthy people take it at low doses like the dose used in this study. Unwanted effects in some people, especially at high doses, may include: headaches, nausea, next-day grogginess or irritability, hormone fluctuations, vivid dreams or nightmares, reduced blood flow, and hypothermia. While no large, long-term studies that might reveal side-effects have been conducted, there are reports about patients having taken melatonin for months without problems. Melatonin can cause somnolence (drowsiness), therefore, caution should be shown when driving, operating machinery, or drinking alcohol.

Where is the study run from?
Bristol Urological Institute (UK)

When is the study starting and how long is it expected to run for?
March 2013 to July 2017

Who is funding the study?
Multiple Sclerosis Society (UK)

Who is the main contact?
Prof. Marcus Drake
Marcus.Drake@bui.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Prof Marcus Drake

ORCID ID

Contact details

University of Bristol and Bristol Urological Institute
Bristol
BS10 5NB
United Kingdom
+44 (0)117 414 7942
Marcus.Drake@bui.ac.uk

Additional identifiers

EudraCT number

2012-004183-21

ClinicalTrials.gov number

Protocol/serial number

13586

Study information

Scientific title

A randomised, double blind, placebo controlled, crossover trial of melatonin for treatment of nocturia in adults with multiple sclerosis

Acronym

Study hypothesis

The aim of this study is to assess the effect of melatonin in patients with Multiple Sclerosis (MS).

Ethics approval

National southwest research ethics committee Exeter, 26/02/2014, ref: 12/SW/0322

Study design

Double-blind randomised placebo controlled crossover clinical trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Home

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Topic: Renal and Urogenital, Nocturia in adults with multiple sclerosis

Intervention

Sustained-release melatonin (‘Circadin’ 2mg taken at bedtime) versus placebo in patients with Multiple Sclerosis.

A run-in phase will be followed by two treatment phases (active drug or placebo) of 6 weeks each separated by a washout interval of 1 month. After the second treatment phase, patients will be entitled to participate in an open label, single-arm extension study of duration one year. Qualitative interviews will be undertaken with participants to assess the impact of nocturia on their quality of life.

Intervention type

Drug

Phase

Not Applicable

Drug names

Melatonin

Primary outcome measures

Added 10/03/2017:
Nocturia episodes per night, measured from a frequency volume chart (FVC) at baseline and at the end of each treatment phase

Secondary outcome measures

Added 10/03/2017:
1. Quality of life, measured with the MS Quality of Life Index (MSQLI), at baseline and at the end of each treatment phase
2. MS disease severity, measured with the MS-specific Expanded Disability Status Scale (EDSS), at baseline and at the end of each treatment phase
3. Urinary tract symptoms, measured with the International Consultation on Incontinence Questionnaires (ICIQ) at baseline and at the end of each treatment phase. ICIQ-MLUTS and ICIQ-FLUTS are gender specific tools for assessing severity and bother of all LUTS
4. Volumes passed when urinating, measured from the FVC at baseline and at the end of each treatment phase
5. Sleep quality, measured with the Pittsburgh Sleep Quality Index (PSQI) at baseline and at the end of each treatment phase

Overall trial start date

25/03/2013

Overall trial end date

08/07/2017

Reason abandoned

Eligibility

Participant inclusion criteria

1. Male and female over 18 years old, upper age limit 80 years
2. Confirmed neurological diagnosis of multiple sclerosis.
3. At least 1 episode of nocturia (as defined by International Continence Society criteria [6]) every night.
4. Female subjects of childbearing potential; willing to use an effective method of contraception throughout the study.

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

UK Sample Size: 50

Participant exclusion criteria

1. Under 18 years old
2. Pregnant patients
3. Symptomatic urinary infection
4. Indwelling urinary catheter
5. Use of desmopressin or investigational medical compounds in the month preceding randomisation
6. Antimuscarinic or diuretic medication, unless used longterm prior to study (at least 3 months) and continued at same dosing regime throughout the study
7. Use of melatonin on prescription, or purchased over the counter/online
8. Use of “sleeping tablets” on prescription, or purchased overt he counter/ online
9. Diabetes mellitus
10. Diabetes insipidus
11. Unwilling to give informed consent
12. Female subjects of childbearing potential; unwilling to use an effective method of contraception throughout the study

Recruitment start date

25/03/2013

Recruitment end date

01/04/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Bristol Urological Institute
Bristol
BS10 5NB
United Kingdom

Sponsor information

Organisation

North Bristol NHS Trust (UK)

Sponsor details

Trust Headquarters
Beckspool Road
Frenchay
Bristol
B16 1JE
United Kingdom

Sponsor type

Hospital/treatment centre

Website

http://www.nbt.nhs.uk/

Funders

Funder type

Charity

Funder name

Multiple Sclerosis Society (of Great Britain & Northern Ireland) (UK) Grant Codes: 959/11

Alternative name(s)

MS Society

Funding Body Type

private sector organisation

Funding Body Subtype

professional associations and societies

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2017 protocol in: https://www.ncbi.nlm.nih.gov/pubmed/28347292

Publication citations

Additional files

Editorial Notes

30/03/2017: Publication reference added. 10/03/2017: The following changes were made to the trial record: 1. The recruitment end date was changed from 25/03/2015 to 01/04/2017. 2. The overall trial end date was changed from 25/03/2015 to 08/07/2017.