Condition category
Digestive System
Date applied
01/12/2009
Date assigned
21/07/2010
Last edited
28/08/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Mr Mark Bignell

ORCID ID

Contact details

c/o Mr Rhodes' Secretary
Department of General Surgery
Norfolk and Norwich University Hospitals NHS Trust
Colney Lane
Norwich
NR4 7UY
United Kingdom

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

Other

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 measures

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

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

c/o Mr Rhodes' Secretary
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

http://www.nnuh.nhs.uk/

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes