Condition category
Respiratory
Date applied
25/02/2014
Date assigned
25/02/2014
Last edited
24/04/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
People cough in order to clear their airways. Most coughs are caused by viruses and settle down by themselves, but some people develop persistent coughing for no reason which can last for many years. This is called chronic cough which is very troublesome and it can have a major impact on the daily life of sufferers. There are very few effective medicines available to treat chronic cough because we don’t fully understand how and why coughing happens. We are doing this research to understand what mechanisms in the body produce coughing and why some people are more prone to developing a chronic cough than others. We will investigate this in this study by testing two different medications. The first one is called Baclofen. Baclofen is a licensed drug which is already used to treat some medical conditions involving the muscles. We already know that Baclofen can also reduce a person’s cough. In this study, we would like to find out if another drug similar to Baclofen can also reduce a person’s cough. The other drug is called Lesogaberan. Lesogaberan is a test medication and is not currently licensed. However, it has already been tested in many trials involving healthy volunteers and patients.

Who can participate?
To improve knowledge of certain diseases, patients and the public are often asked if they would like to be involved in research studies. This study is open to healthy individuals aged 18 to 70 years.

What does the study involve?
Taking part involves five visits to the University Hospital of South Manchester NHS Foundation Trust. Participants will be required to perform a capsaicin challenge test (designed to make a person cough), and undergo safety tests which include blood tests, urine tests (women only) and electrocardiograms (ECGs). Participants will also be given tablets containing Baclofen and Lesogaberan on separate occasions. They will also be given a tablet called a placebo. A placebo is a substance that looks the same as the study medicine but it does not contain any active ingredients, it is a ‘dummy’ drug. Neither the study participants nor the researcher will know which drug has been given at each treatment visit. The order of treatment will be allocated at random (like tossing a coin).

What are the possible benefits and risks of participating?
There will be no direct benefit to participants by taking part in this study. However, we hope that the information we get from this study will help to improve treatment of cough in the future. Baclofen is a licensed drug which is used widely. The most common side effects reported by people taking Baclofen are drowsiness, light-headedness and headache. Lesogaberan is an unlicensed study medication but it has already been tested in several studies involving both healthy volunteers and patients and has been found to be well tolerated. The main side effect experienced by some people is a short-lasting feeling of ‘pins and needles’. During the study participants will be asked to perform a cough challenge test which involves inhaling capsaicin, a component of chilli peppers. Capsaicin can cause tightening of the airways, although this is rare. Breathing tests are performed during and after the test to monitor any chest tightening, which is easily treated by inhaling salbutamol (a medication to open up the airways).

Where is the study run from?
This study is taking place at the University Hospital of South Manchester NHS Foundation Trust.

When is the study starting and how long is it expected to run for?
The study started in January 2014 and will run until April 2014.

Who is funding the study?
Medical Research Council (UK).

Who is the main contact?
Dr Demi Valdramidou
demi.v@manchester.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Ms Dimitra Valdramidou

ORCID ID

Contact details

Wythenshaw Hospital
Wythenshawe Hospital
Southmoor Road
Manchester
M23 9LT
United Kingdom
demi.v@manchester.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

14999

Study information

Scientific title

The Role of GABAB Receptor Mechanisms in Cough: Effect of Lesogaberan, Baclofen and Placebo on Experimentally Induced Cough Responses in Healthy Controls

Acronym

GARMIn

Study hypothesis

Cough is a protective reflex which is used to clear the upper airways of irritating material or mucus (phlegm) and yet it is the most common complaint for which people seek medical advice. Most coughs are caused by an infection, such as a cold, which usually settles within 8 weeks. However, some people develop persistent coughing which can last from 8 weeks to several years. This persistent cough is known as ‘chronic cough’. Chronic cough is a common and troublesome problem and is associated with poor quality of life. Effective, well-tolerated treatments for cough remain a significant unmet need which may be due to the poor understanding of the mechanisms which underlie cough in humans. This research has therefore been designed to improve our understanding of the mechanisms that control the human cough reflex by investigating whether two drugs which act of different parts of the nervous system reduce coughing in a similar way.

In this study we aim to recruit 15 healthy volunteers to attend the University Hospital of South Manchester NHS Foundation Trust on five separate occasions. During study visits participants will be given either lesogaberan, baclofen or placebo in a randomised order, perform a capsaicin cough challenge test and undergo safety monitoring including blood tests, liver and kidney function tests, and electrocardiograms.

More details can be found at: http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=14999

Ethics approval

NRES Committee North West – Haydock, 22/10/2013, 13/NW/0715

Study design

Randomised; Interventional; Design type: Treatment

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

Topic: Respiratory; Subtopic: Respiratory (all Subtopics); Disease: Respiratory

Intervention

Baclofen, central acting GABA-B receptor agonist (mechanistic use), 40 mg, oral tablet
Placebo, 40 mg, oral tablet

Lesogaberan, peripheral acting GABA-B receptor agonist (mechanistic use), 120 mg, oral tablet
Placebo, 120 mg, oral tablet

Each study treatment will be taken during the study visit and will consist of a single capsule (lesogaberan 120 mg or matched placebo) and a single tablet (baclofen or matched placebo).

Total duration of treatment is five visits (maximum 5 hours per visit) over a 4-week period.

There is no planned follow-up visit after the final study visit.

Intervention type

Drug

Phase

Not Applicable

Drug names

Baclofen, lesogaberan

Primary outcome measures

Emax of Lesogaberan V placebo; Timepoint(s): Change in the maximal number of coughs (Emax) evoked by inhaled capsaicin

Secondary outcome measures

1. ED50 of Lesogaberan V placebo; Timepoint(s): Dose of inhaled capsaicin inducing at least half of maximal cough frequency (ED50)
2. Emax of Lesogaberan V Baclofen; Timepoint(s): Change in the maximal number of coughs (Emax) evoked by inhaled capsaicin

Overall trial start date

09/01/2014

Overall trial end date

30/04/2014

Reason abandoned

Eligibility

Participant inclusion criteria

1. Provision of signed, written and dated informed consent, prior to any study-specific procedures
2. Aged 18 to 70 years
3. Body mass index (BMI) of between 19 and 30 kg/m2 (inclusive) and weight between 50 kg and 100 kg
4. Normal spirometry
5. Clinically normal physical findings
6. Subjects with no concurrent diseases who do not require any medication
7. Female subjects with no childbearing potential or using highly effective method of contraception for at least the previous 3 months
Target Gender: Male & Female; Upper Age Limit 70 years ; Lower Age Limit 18 years

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 15; UK Sample Size: 15

Participant exclusion criteria

1. History of any clinically significant disease or disorder, in particular no current or past history of chronic cough or respiratory disease.
2. History or presence of gastrointestinal, hepatic or renal disease
3. Any clinically significant illness, medical or surgical procedure or trauma within 4 weeks of the first administration of study medication
4. Any clinically significant abnormalities in clinical chemistry, haematology or urinalysis results Abnormal screening laboratory values in Liver Function tests
5. History of clinically significant orthostatic reaction or syncope
6. Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG according to the investigator
7. Prolonged QTcF>450ms or family history of long QT syndrome

Recruitment start date

09/01/2014

Recruitment end date

30/04/2014

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Wythenshaw Hospital
Manchester
M23 9LT
United Kingdom

Sponsor information

Organisation

University Hospital of South Manchester NHS Foundation Trust (UK)

Sponsor details

Wythenshawe Hospital
Southmoor Road
Wythenshawe
Manchester
M23 9LT
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Research council

Funder name

Medical Research Council (MRC) (UK) Grant Codes: MR/K015141/1

Alternative name(s)

MRC

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

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

Publication citations

Additional files

Editorial Notes