People across Hampshire, Dorset and Wiltshire are being invited to take part in a national trial of Irritable Bowel Syndrome (IBS).
University of Southampton Doctors are testing 'low-dose amitriptyline' - the drug is recommended for people with persistent IBS symptoms.
The study will recruit over 500 people with the disease, who will either receive the treatment or a placebo tablet.
IBS affects 1 in 10 people - the research is funded by the National Institute for Health and is due to be completed in June 2022.
In Southampton and the South, they are aiming to recruit 175 patients from 25 GP practices.
The University of Southampton's Highfield Campus
The drug is thought to work at low doses in IBS because it has pain-relieving properties and changes bowel activity.
In addition to the South, participants will be recruited from general practices within Yorkshire and the South West of England.
Co- Chief Investigator Hazel Everitt, Professor of Primary Care Research at the University of Southampton said: "We know that many people with IBS have troublesome ongoing symptoms which are not helped by ‘first-line’ prescribe medications such as laxatives.
"Low dose amitriptyline is recommended as a ‘second-line’ option but is currently not often prescribed by GPs.
"This trial will provide GPs and patients with evidence to know whether it may help people with IBS in primary care."
Co- Chief Investigator Alexander Ford, Professor of Gastroenterology at the University of Leeds, states: “Ours will be the first large study to whether they work in this setting.
"The work is therefore of considerable importance for people living with IBS, their families, the NHS, and society as a whole.”