Re-launching clinical trials during a pandemic; ATLANTIS study resumes to explore links between antidepressants and IBS treatment
An interview with:
- Professor Alexander Ford, Professor of Gastroenterology and Honorary Consultant Gastroenterologist - Leeds Institute of Biomedical and Clinical Sciences, University of Leeds and Leeds Gastroenterology Institute, Leeds Teaching Hospitals Trust
- Professor Hazel Everitt, Professor of Primary Care Research - Primary Care Research Centre, School of Primary Care, Population Sciences and Medical Education (PPM) - University of Southampton
The ATLANTIS Study has been a long time in the making. 12 years ago, during post-doctoral study in Canada, Alex was involved in an Irritable Bowel Syndrome (IBS) study.
While working on the study, his research highlighted that numerous other studies had examined the potential link between using tricyclic antidepressants to help manage IBS symptoms but the evidence and results from those studies was ambivalent. The links were there, but the data hadn’t been collected properly.
“After deconstructing all of the previous analysis, it was clear it hadn’t been done very well,” says Alex. “The trial control arms had been muddled up. So we re-synthesised the data and were able to show a definitive link between the use of the drugs and a reduction in IBS symptoms.”
The work was published in the journal Gut and cited many times. It’s reached NICE guidelines as a “consideration” for treatment for patients with IBS, but the adoption of tricyclic antidepressants for IBS has made slow progress.
Previous studies have looked at the use of them in secondary and tertiary healthcare settings. The ATLANTIS Study is assessing the use of the drugs in a primary care setting, where it is currently little used for IBS, to establish the overall effects on patients and their wellbeing.
“I had my first study proposal turned down by the Health Technology Assessment (HTA) programme,” explains Alex. “I knew it was important research so I approached Hazel as she’d been working in IBS research for a while. Having more expertise and a wider knowledge base was going to be essential to the trial’s success. As it turned out, it then got rejected a second time by the HTA.”
Both Hazel and Alex knew that the research was important, so they continued to push for the trial to go ahead, this time approaching the Research For Patient Benefit (RFPB) programme, but were turned down again.
Fortunately, the HTA then commissioned a study into the use of antidepressants for IBS. Nine years on since the first idea for the trial, Hazel and Alex are finally recruiting participants and collecting data.
This hasn’t come without its own set of challenges, however. When the trial began in December 2019 things were on the up. But the coronavirus pandemic stopped the recruitment process in its tracks in March, with only around 50 participants assessed and randomised out of a target of 518.
“There are lots of steps to get people involved in this trial,” explains Hazel. “We have to approach and recruit GPs to take part and identify patients who could be eligible.
"The GPs are trained in the trial procedures and then letters are sent to invite patients. Interested patients have a screening phone call for initial eligibility and then a blood test at the practice. If the bloods and final screening are OK they then complete a baseline questionnaire before they can be accepted on to the trial. As you can imagine, lockdown had a huge impact on our ability to do a lot of this work.”
The first step was to make sure that the participants already recruited and randomised were able to maintain their supply of the trial drugs from the pharmacy and that participant safety procedures continued e.g. emergency unblinding of drug allocation if needed. The trial nurses then contacted all participants to confirm the trial could continue safely.
Some follow up forms and study surveys were paper-based and unable to be accessed at the Clinical Trials Unit in Leeds, so fully electronic data collection was put in place so participants’ data could still be gathered during lockdown.
Screening calls went ahead for patients who had already expressed an interest in taking part, but as there was no access to GP surgeries the next steps of recruitment were placed on hold.
Once lockdown began to ease, Alex, Hazel and the study team had to re-visit many of their procedures and paperwork. The study had to be re-evaluated in order to safely restart and get back into GP surgeries. Sourcing PPE, reviewing standard operating procedures and assessing spaces in GP surgeries all created additional workload before the trial could begin again.
“We couldn’t do this study without the dedicated team of research nurses that are allocated to the trial,” says Hazel. “Having their skills, knowledge and flexibility to adapt procedures has allowed the trial to keep going, especially during this really challenging time. We are very lucky to have them available to us.”
Throughout lockdown, participants remained engaged and keen to be involved – even those who were put on hold. The study has now been re-launched, as of September 2020, and has 127 participants registered, 103 of them randomised.
“It’s so important that non-COVID trials keep going,” emphasises Alex. “Because we can’t let other research get neglected. It will cause so many bigger problems further down the line.”
The double-blind placebo-controlled trial will be ongoing until July 2022 with participants recruited for a six month period on the trial medication, with an option to continue it out to 12 months.
Alex explains: “Most drug trials for IBS are 12 weeks long, so we wanted to meet that but also take into account that IBS is a chronic condition. Assessing patients over a longer period will allow us to measure more of the overall impact on symptoms and quality of life.”
There is hope that a successful outcome of the trial could help patients with symptom control, in a painful and socially-limiting chronic condition that has few treatments available that are widely effective. It could also change primary care management of IBS and help to ease pressure on secondary care services in the NHS and reduce referrals.
“Around 10-25% of gastroenterology in secondary care is IBS,” says Alex. “So if we can show that this treatment is cost effective and works for milder symptoms, we will hopefully be able to demonstrate impact on reductions in referrals, blood tests and investigations.”