Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
Nalcol01
Study information
Scientific title
Naloxone hydrochloride SR gastro-resistant sustained release capsules as a treatment for functional constipation: a randomised, double-blind controlled trial in secondary care
Acronym
Study hypothesis
The primary objective of this study is to assess the efficacy of Nalcol™ when used as an adjunct to usual laxatives in the treatment of patients with refractory chronic constipation. The null hypothesis states that there will be no improvement in the symptoms of constipation in those participants taking Nalcol™ compared to the placebo group.
Ethics approval
Cambridgeshire 1 Research Ethics Committee, ref: H09/0304/55
Study design
Single-centre double-blind randomised parallel-group study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Constipation
Intervention
This is a single-centre double-blind placebo-controlled study of the efficacy and safety of Nalcol™ given to patients with refractory constipation attending a specialist clinic. The study is principally a phase II trial of short-term (4 weeks) effect. It is suspected that Nalcol™ will have a moderate effect, and is used here as an adjuvant to regular laxatives.
The patients will all fulfil criteria for functional constipation (as above) and will have attended a specialist gastroenterology or colorectal clinic at the Norfolk and Norwich University Hospital. They will have undergone investigation for their constipation with barium enemas and also transit studies and their basic management, including dietary and lifestyle advice and modification of laxatives, will have been instigated.
The key treatment phase (Period 2) will last 4 weeks and data over 4 weeks of treatment will be available. Two weeks of pre-treatment data will be collected during the screening period before randomisation (Period 1). This will allow an assessment of patient suitability and health to ensure that the inclusion criteria are met and permit examination with a rigid sigmoidoscope to obtain a rectal biopsy and stool sample. This initial period will ensure short-term symptom stability and confirm patient compliance with diary completion. It will allow secondary analyses comparing pre-treatment and treated symptom scores and quality of life (QoL) data. A final phase of 4 weeks (Period 3) will allow all patients in the trial to evaluate the treatment and provide further observation over a more prolonged duration.
Nalcol™ is given to relieve symptoms, which may be variable from day-to-day. The tolerability of Nalcol™ tablets is expected to be comparable to that of commonly dispensed stimulant laxatives; with no significant systemic side effects. It is known that 10 mg, twice a day is effective in increasing gut motility in normal subjects and a group of patients have taken 40 mg daily and occasionally up to 60 mg daily for severe symptoms. 40 mg daily has therefore been chosen to be given to patients in this trial because of the very troublesome symptoms of constipation from which they suffer.
Intervention type
Drug
Phase
Phase II
Drug names
Naloxone hydrochloride (Nalcol™)
Primary outcome measure
Comparison of the responders during Period 2 of the study (weeks 3 - 6) in the treatment group and those in the placebo group. Response is defined as those participants who give an assessment of 'satisfactory improvement' on at least 50% of occasions over the 4-week trial period (Period 2) to the global question on the diary card.
Secondary outcome measures
1. Comparison of stool frequency and type, laxative use, Patient Assessment of Constipation Symptoms (PAC-SYM), and Patient Assessment of Constipation Quality of Life Questionnaire (PAC-QOL) between treatment and placebo groups during Period 2 of the study. PAC-SYM will be used to provide an overall symptom score; but each component will also be analysed separately to identify changes to individual symptoms. Comparison will be made between the pre- and post-trial transit study as an objective marker of a reduction in transit time.
2. Graphical representation of the temporal changes in stool frequency and type and analysis to assess any drop-off of effect after 8 weeks of use in those receiving Nalcol™ for 8 weeks or in the whole group
3. A comparison of pre-treatment versus treatment symptom levels in the whole (n = 120), i.e., Period 1 versus Period 3
4. Comparison of stool bacterial counts between the treatment and placebo groups in the selected subset after each Period
Overall trial start date
01/02/2010
Overall trial end date
01/02/2012
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Aged greater than 18 years
2. Male or female
3. Satisfy Rome III criteria for functional (slow transit) constipation
4. Symptoms not relieved by diet and laxatives
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
120
Participant exclusion criteria
1. Severe cardiac, renal or hepatic impairment
2. Severe psychiatric disturbance
3. Mental disorder preventing adequate informed consent
4. Dilatation of the bowel (megarectum or pseudo-obstruction)
5. Concomitant medication with drugs known to cause constipation
6. Known pregnancy, suspected pregnancy, or trying to conceive
7. Currently breastfeeding
8. Currently participating (or within 1 month) in any other study
Recruitment start date
01/02/2010
Recruitment end date
01/02/2012
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Norfolk and Norwich University Hospitals NHS Trust
Norwich
NR4 7UY
United Kingdom
Sponsor information
Organisation
Norfolk and Norwich University Hospitals NHS Foundation Trust (UK)
Sponsor details
c/o Kath Andrews
Research and Development Office
Colney Lane
Norwich
NR4 7UY
United Kingdom
Sponsor type
Government
Website
Funders
Funder type
Government
Funder name
Norfolk and Norwich University Hospitals NHS Foundation Trust (UK) - research account (ref: E-31)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
SLA Pharma AG (Switzerland) - provide active and placebo capsules
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
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
Basic results (scientific)
Publication list