Published: 31 May 2023

HRB invests €10.2 million to continue developing a thriving clinical trials ecosystem in Ireland

12 new awards in the latest round of the HRB’s Definitive Intervention and Feasibility Award (DIFA) scheme will support research in areas including cancer, type-1 diabetes, speech and language therapy for pre-schoolers, and pain management following spinal cord injury.

DIFA is central to the HRB’s strategic objective of developing a thriving clinical trials ecosystem in Ireland. More detail on each new award under the 2023 scheme, including lay summaries, is available below.

According to HRB Chief Executive, Dr Mairéad O'Driscoll:

“We are proud to announce the latest round of funding in the HRB’s DIFA scheme. It is the only public funding source for investigator-led clinical trials in Ireland. Not only will DIFA enhance our country’s reputation as a location for high quality clinical trials, but it will also help to realise the HRB’s ambition of a people-centred Irish healthcare system where access to clinical trials is routine to standard care.”

The investment includes seven Definitive Intervention (DI) and five Feasibility awards.

• Funding for each DI is approximately €1.2M over 5 years and 
• Funding for each Feasibility award ranges from €360k - €400k over 3 years. 

The 2023 call is the fourth round of the DIFA scheme, bringing the total number of awards funded by it to 45, and an overall investment by the HRB of approximately €32 million. 

According to Oonagh Ward, Head of Research and Innovation Infrastructures at the Health Research Board (HRB):

“Three aspects of these awards are particularly rewarding. Firstly, all 12 awardees are connected to established HRB-supported clinical trials infrastructures. Secondly, seven out of the 12 projects incorporate Studies within a Trial (SWAT) components, seeking to further understand trial methodology. Thirdly, two* of the DI awards originated from previously HRB-funded feasibility studies. These achievements demonstrate the strategic development of a cohesive clinical trials ecosystem by the HRB, where all the different components synergistically interact.”

The 2023 awards were selected via a rigorous two-phase application and assessment process, which included international peer review, public review, and review by an international panel of experts. 
56 applications were received at pre-application stage. Following review by a Standing Panel of International experts, 29 applications (13 DI’s and 16 Feasibility Studies) were invited to submit a Full Application. Assessment criteria included the case for the study; appropriate methodology and feasibility of the study; and potential for impact.   

Ends.

*The two previously funded Feasibility awards were by Prof Sean Dinneen (2017) and Dr Sinead Hynes (2018).

For more information on the HRB’s significant strategic investment in clinical trials infrastructure, please see the below links: 

• A coordinated clinical trials ecosystem in Ireland – are we there yet?  
• International Clinical Trials Day 2022: HRB investment of €155 million for a world class clinical trials ecosystem in Ireland – an overview

Definitive Intervention and Feasibility Awards (DIFA) 2023 - Awardees

Listed by Host Institution, then alphabetically by title.

1. A randomised controlled pilot trial of psilocybin with psychological support for cocaine use disorder 

Lead Applicant: Dr John Kelly 
Host Institution: Trinity College Dublin 
Study Type: Feasibility Study 

Lay summary: Cocaine use disorder is a condition which causes damage and distress to an individual through their cocaine use. It can also cause major problems for their families and for society. There are currently no medical treatments for it specifically. This study will explore the use of psilocybin to treat cocaine use disorder.  
Psilocybin, the active ingredient of ‘magic mushrooms’, has been shown over the last two decades to be a potential treatment for a range of disorders. It is a once-off treatment given in the context of short-term supportive psychotherapy.  
Psilocybin works on the serotonin system in the brain, the chemical that can regulate your mood, anxiety, motivation and impulse control. A growing number of clinical trials are showing that psilocybin with psychological support offers a promising treatment option for alcohol and tobacco addiction, while others show improvements in mood, anxiety, quality of life, and sense of connectedness. We know very little, however, about whether it will work for people with cocaine use disorder.  
In preparation for a large trial, this will be a smaller preliminary pilot trial to gather information, running over fifteen weeks. We aim to recruit 24 people with cocaine use disorder. They will receive 3 sessions of psychological support with a trained therapist before receiving psilocybin 25mg or diphenhydramine 100mg (placebo), and 3 sessions after receiving psilocybin or placebo. Participants and the researchers will not know which dose each person will receive. Participants will complete questionnaires during study visits to assess cocaine use and cravings, together with mood, anxiety, quality of life, and sense of connectedness.  
We hope this preliminary study will pave the way for a larger study to assess if psilocybin with psychological support will promote cocaine abstinence, reduce craving, and reduce rates of relapse in people with cocaine use disorder. 

2. Examining the effectiveness, and cost-effectiveness, of a Work and Cancer self-management programme to support women with breast cancer to return to work 

Lead Applicant: Dr Deirdre Connolly 
Host Institution:  Trinity College Dublin 
Study Type: Definitive Intervention 

Lay summary: Women with breast cancer make up a significant proportion of cancer survivors, with more than 43,750 women living with breast cancer in Ireland. However, many women report physical and psychological health difficulties that interfere with their ability to return to work. In Ireland, and internationally, these difficulties are being increasingly recognised, with recent research identifying gaps in support programmes to prepare women with breast cancer to return to work. Collaborating with women with breast cancer, and those who provide health and supportive services to individuals living with cancer in Ireland, we co-designed an online Work and Cancer programme. This programme aims to support women with breast cancer to manage the process of returning to work and learn strategies to manage post-treatment health-related difficulties. The programme also provides information on workplace entitlements. The Work and Cancer programme was trialled with women with breast cancer in 2021, who reported that the programme gave them confidence to return to work and that the content was relevant. We now want to test the programme with a larger group of women with breast cancer to determine if it is effective in supporting return to work. To do this, we will include 248 women in the study, half of whom will receive the programme and we will compare their results with women who do not receive the programme. Women who receive the programme will be interviewed to explore if it helped them to return to work. Having a programme that is financially viable is important and therefore the costs involved in running and attending the programme will also be calculated. Should this study demonstrate that the Work and Cancer programme is effective in supporting women with breast cancer to return to work, we will collaborate with cancer services in Ireland to make the programme available nationally. 

3. Medicines and SocIal Prescribing to aDdress pAtient priorities in multimorbidity (MIDAS): A multi-arm definitive cluster randomised trial in Irish general practice 

Lead Applicant: Professor Susan Smith
Host Insitution: Trinity College: Dublin 
Study Type: Definitive Intervention

Lay summary: Multimorbidity is a term for the experience of living with two or more ongoing/long-term health conditions. This has a big impact on patients and health systems, and approaches are needed to support patients living with multiple conditions and the doctors and nurses providing their care. We previously did two smaller studies of such approaches; one provided pharmacist support to GPs to manage medicine prescribing (MyComrade), and the other provided support from link workers (community health workers with training in identifying. health and social care needs) who address patient aims and needs and connect them to community services (LinkMM).  

Our study will happen in 48 diverse general practices, which will be divided by chance into one of three groups. Each practice will be assigned to either pharmacist support (MyComrade), link worker support (LinkMM) or to continue with care as usual acting as a comparison. Patients with 2+ chronic conditions taking 10+medicines in these practices will be asked by GP nurses to join the study when they attend their chronic disease management review. If interested, they will sign consent and in MyComrade and LinkMM practices, the GP nurse will arrange for pharmacist or link worker support.  
They will also complete confidential questionnaires throughout the study on their wellbeing, mental health, quality of life, experience of care, and confidence managing their conditions. 
This information, and general health service usage and cost data, will help us understand whether the pharmacist or link worker improve outcomes. The design of this study is supported by a Patient and Public Involvement group with specific experience in studies examining multiple conditions. They will stay involved throughout to ensure we conduct research that matters to patients. This large-scale national study will provide much needed information on how to improve care delivery and outcomes for people with multiple conditions 

4. Semaglutide for people with obesity and resistant hypertension trial (SUPPORT): a pilot randomised, double blind, parallel group, integrated, multicentre clinical trial  

Lead Applicant: Professor Martina Hennessy 
Co-Lead Applicant: Dr Cormac Kennedy
Host Institution: Trinity College Dublin 
Study Type: Feasibility Study & SWAT 

Lay summary: This study asks the question "does lowering weight using a drug called semaglutide given by injection reduce high blood pressure (BP) in patients with poorly controlled BP and excess body weight (obesity)". This is important because although we know high BP can lead to serious health problems such as a heart failure, we have not considered BP management from the viewpoint of weight reduction before. The risk of heart disease from high BP is reduced by medicines, but they don't work for everyone and multiple drugs may be needed. This is called resistant hypertension and it is associated with excess weight. By reducing weight we expect the BP will reduce, as well as the risk of an unhealthy heart.  
To test this idea, suitable people with high BP and weight are invited into the study. If they agree, their weight, height and BP are measured and volunteers are trained to self-inject the study medicine. To test the medicine, every second person involved will get the active medicine, while the other will get a similar looking but inactive liquid. The medicine is considered safe and may help the person lose weight. Advice about a healthy lifestyle is provided. When beginning treatment, blood tests are taken, BP and weight are measured and participants are asked to answer questionnaires. Weight and BP will be measured every 12 weeks thereafter, with repeat blood tests and questionnaires at the end of the study (36 weeks). These may be completed online or during a doctor’s visit.  
This pilot study will inform how a larger study can be best planned and delivered as part of routine hospital or GP care. Ultimately, this will help us to understand whether weight lowering medicines can be used to improve difficult to control blood pressure, health and well-being.

5. Implementing a targeted selective speech, language, and communication intervention at scale - the case of Happy Talk

Lead Applicant: Dr Pauline Frizelle
Host Institution: University College Cork
Study Type: Definitive Intervention & SWAT

Lay summary: Research has shown that there is a large gap between the speech and language skills of 40 – 50% of preschool children from poorer backgrounds compared to those who are wealthier. To try and reduce this gap speech and language therapists (SLTs) have taken several treatment approaches. One approach is to teach parents the best way to talk and interact with their children so that they can help them develop better speech and language skills in everyday situations. Another approach is to train staff working with young children in early years settings how to create the best language learning opportunities for them. Studies have looked at the effects of both of these approaches, but few studies have examined the effects when therapists work with parents and staff at the same time. In addition, there is a shortage of research studies carried out in the ‘real world’ where the treatment is given by practicing SLTs rather than a team of university-based researchers. We recently carried out a ‘real world’ study on ‘Happy Talk’, a community-based programme in which SLTs work together with parents and preschool staff at the same time. We found that Happy Talk had a large positive effect on children’s understanding of language and a medium effect on their overall language skills, compared to children who didn’t receive the programme. We also found ‘Happy Talk’ to be cost-effective. The proposed study aims to build on this by 1) completing a much larger study where children’s allocation to the programme will be decided randomly and where we will look at costs and benefits on a larger scale; 2) identifying key features that support successful application of the programme in the real world and incorporating these into future roll-outs; 3) learning how to make Happy Talk work in a range of contexts

6. BRAIN OXYGEN NEUROMONITORING ASSESSMENT (BONANZA) EUROPE TRIAL; a multicentre, randomised phase III trial of brain tissue oxygen (PbtO2) monitoring versus standard care after severe TBI 

Lead Applicant: Professor Patrick Murray 
Host Institution: University College Dublin 
Study Type: Definitive Intervention & SWAT 

Lay summary: Brain injury which occurs due to trauma (traumatic brain injury) is a leading cause of death and disability and particularly affects young people. Six months after their injury, 25% of patients have died and 25% cannot live independently.  
Importance of Brain Oxygen Levels. After the primary brain injury (e.g. car accident), additional brain damage often occurs, so called ‘secondary brain injury’, which can significantly affect patient survival and disability. While we often can’t prevent the primary injury, we can try to minimise this secondary brain injury. The brain requires a continuous adequate supply of oxygen. Patients who die or have significant disability after a traumatic brain injury often have had low levels of oxygen in the brain. There are common interventions that can normalise the brain oxygen levels. However, none of the standard monitoring devices routinely used in the intensive care unit (ICU) actually measure brain oxygen levels meaning that these potentially ‘reversible’ low levels of brain oxygen go unnoticed and untreated.  
BONANZA study. In the Brain Oxygen Neuromonitoring Assessment (BONANZA) study patients’ brain oxygen levels will be monitored and when a low level of oxygen is detected, we will provide treatments in an attempt to bring the brain oxygen levels back to normal. We believe this close monitoring and ICU intervention to improve brain oxygen levels will reduce the amount of death and disability 6 months after injury. We have received funding and have commenced this study in Australia. We are applying for funding to conduct this study in Ireland and our European hospital network.  
Need and Impact. If BONANZA reduces death and disability in traumatic brain injury patients this would have a significant positive impact on patients, their families, healthcare costs and society as a whole, changing clinical practice globally. 

7. Exoskeleton Training for Spinal Cord Injury Neuropathic Pain: A Phase 2 Feasibility Randomised Trial 

Lead Applicant: Dr Olive Lennon 
Host Institution: University College Dublin 
Study Type: Feasibility Study 

Lay summary: Spinal cord injury is associated with significant disability and health complications including bowel/bladder and respiratory problems. What is not as well known is that up to half of all people with a spinal cord injury develop severe nerve pain called neuropathic pain. In people well-adjusted to their injury this is their biggest health concern that they often say is more distressing than the injury itself.  
Neuropathic pain is thought to result from overactivity in some sensory nerves and/or abnormal changes in the body's representation in the brain because of the sensory and motor loss following injury. Neuropathic pain is mostly treated with medications to reduce pain intensity (anti-convulsants (called pregablin and gabapentin), antidepressants (amitriptyline), anti-inflammatories, opioids and paracetamol). These can reduce pain levels by up to 50% but only in 1 out of 3 of people [Guy et al 2016]. Side-effects and fear of medication dependency mean people often stop medication and request treatments that are not tablet-based.  
Stimulation of inactive parts of the brain using imagined movements and/or sensations or "tricking the brain" using virtual waking environments have shown promise for reducing nerve pain intensity after spinal injury. Despite many studies examining imagined movements and their effect on nerve pain in spinal injury, the use of actual walking using robotic assistance has not been studied well. Very few studies, with limited scientific contribution exist, although animal studies of walking (locomotor) training in spinal cord injury have shown good effect in preventing and/or reversing this type of nerve pain.  
This study asks is providing walking practise three times a week by means of a robotic device called an exoskeleton possible to deliver? Would people sign up and stick to the programme? And might it help reduce pain levels after spinal cord injury? 

8. REMAP-CAP (Randomised, Embedded, Multi-factorial, Adaptive Platform Trial for Community Acquired Pneumonia) Ireland 2023: Beyond COVID-19 

Lead Applicant: Professor Alistair Nichol 
Host Institution: University College Dublin 
Study Type: Definitive Intervention & SWAT  

Lay summary: Community Acquired Pneumonia- a major public health problem. Community-acquired pneumonia (CAP) is a lung infection caused by a bacteria or viruses e.g., COVID-19, influenza. When severe, it can lead to intensive care unit admission, lung failure and death. It is the 4th leading cause of death worldwide (WHO, 2019). 
An Overactive Immune Response. CAP causes a protective immune response (inflammation). This immune response releases molecules called ‘cytokines’. However, overactive release of these cytokines causes changes in the endothelium barrier (cells lining the lung) leading to lung failure and injury to other organs. We showed that treatments which reduce this immune response were found to reduce death and illness in patients with CAP caused by COVID-19.
The REMAP-CAP-Ireland trial. REMAP-CAP-Ireland is an international clinical trial testing treatments for CAP. We will test three potentially new treatments. Firstly, we will test two treatments ‘tocilizumab’ and ‘baricitinib’ which reduce inflammation caused by cytokine molecules. These drugs may be particularly beneficial for CAP caused by influenza virus (where this overactive-immune response occurs, like in COVID-19). Secondly, we will test ‘imatinib’ which targets and protects the endothelium cells lining the lung to determine if it reduces death from any cause of CAP (bacterial, viral).  
We will conduct this trial across hospitals in Ireland led by the HRB-Irish Critical Care-Clinical Trials Network and contribute to this study globally. REMAP-CAP is ground-breaking with many novel design features. It is adaptive (learns from its results and can test new treatments rapidly), it can test multiple treatments simultaneously, it continually examines results to see if a treatment is beneficial and which combinations are best. It has already effectively delivered 11 treatment recommendations for COVID-19, defining treatment globally and saving thousands of lives.  We now want to test if these treatments further improve outcomes in critically ill patients with CAP. 
 

  
9. A Cognitive Occupation-Based programme for people with Multiple Sclerosis: definitive trial (COB-MS) 

Lead Applicant: Dr Sinead Hynes 
Host Institution: University of Galway 
Study Type: Definitive Intervention & SWAT 

Lay summary: Cognitive problems, like not being able to hold a conversation or remembering where you left your keys, are common symptoms experienced by people living with multiple sclerosis (MS). The effect can be wide reaching, from the struggle to remain in the workplace to self-care. The healthcare professional who usually treats the patient, through assessment and treatment, is the occupational therapist. There has been no occupational therapy treatment developed and tested for the control of this devastating symptom until the development of the COB-MS. A feasibility study tested the COB-MS intervention. The occupational therapists and people living with the condition were positive about the COB-MS. Based on this result, we want to know the clinical effect of the therapy and its cost-effectiveness, compared to usual care (control group). This study will have three groups - online COB-MS, in-person COB-MS, and usual care. We conducted the feasibility study online, because of the COVID-19 pandemic, and now we want to check both an online and in-person delivery of COB-MS. We will use five separate work packages in this trial.   

• WP1: A small scale study of the COB-MS to test everything. 
• WP2: Evaluation of the COB-MS through collecting outcomes from participants. 
• WP3: COB-MS cost-effectiveness analysis. 
• WP4: We will assess if the programme was followed correctly and in what context.   
• WP5: Two studies focused on outcomes and retention to be carried out.  

This project will focus on critical priorities in MS recovery, occupational therapy and trial methodology. By including the MS community (with a strong PPI focus) and experts in trial methodology, health economics, statistics, and health service research, we hope to improve the quality of life of people with MS nationally and internationally. This therapy could also reduce the cost to society, and economies, as well as helping those living with distressing cognitive challenges.

10. The D1 Now intervention to improve outcomes in young adults living with type 1 diabetes: A definitive cluster randomised controlled trial 

Lead Applicant: Professor Sean Dinneen
Host Institution: University of Galway
Study type: Definitive intervention and SWAT

Lay summary: Type 1 diabetes is a challenging condition to live with, involving many daily tasks such as administering insulin and checking blood sugars. It is hard to balance diabetes management with the demands and unpredictability of being a young person. This means that young adults with diabetes often stop attending their clinic appointments and may struggle with diabetes management. 
Since 2014, our research team and Young Adult Panel have worked together to develop a new intervention that can be used in clinic appointments. This intervention is called ‘D1 Now’ and it has two parts  

1. Agenda Setting Tool - a form used by young adults and healthcare professionals to identify topics to discuss and set goals together  
2. Support Worker - a buddy for young adults who is present at every clinic appointment and can be contacted in between appointments  

From 2019-2021 we tried out a version of the D1 Now intervention in a pilot. We wanted to find out if the intervention was acceptable. Young adults and staff members liked the intervention, but some small changes were needed. We have made these changes and now want to figure out if the D1 Now intervention could improve outcomes relating to diabetes and quality of life.  
To do this, we need to test it out in a Randomised Controlled Trial. We will need 12 diabetes centres. We will randomly pick 6 of them to use the intervention for one year. The other 6 will keep doing their usual practice. Afterwards we will test to see if the young adults in the 6 intervention centres have better outcomes. We will also do interviews with the participants involved to see what they think about the intervention. We will share our findings in journal articles, conference presentations, blog posts and social media posts. 

11. SalT supplementation in Older adults with Orthostatic intolerance Disorders (STOOD): a phase IIa randomised controlled trial of sodium supplementation in those consuming moderate salt intake. 

Lead Applicant: Professor Andrew Smyth 
Host Institution: University of Galway 
Study Type: Feasibility Study 

Lay summary: Falls are a leading cause of disability and death in the elderly. One of the main causes of falls are sudden drops in blood pressure upon standing, a condition called orthostatic hypotension (which means low blood pressure on standing), which affects one in five older adults. This condition can cause symptoms (e.g., dizziness and fatigue) and makes it difficult to manage daily tasks that require standing for a long time (e.g. cooking) or stooping (e.g. dressing).  
Currently, the most common treatment for this condition is large increases in salt intake, which is recommended by most leading expert guidelines to manage orthostatic hypotension. However, this recommendation is based on very little research, and that research is of poor quality. In fact, the recommendation is really based on the assumption that it works, rather than proven to work. The added concern is that we now know that long-term high salt intake is bad for the heart, and increases the risk of heart attacks and stroke over years and the elderly appear to be especially vulnerable. The small amount of research done on high salt intake to treat orthostatic hypotension has only looked at short-term effects (4-6 weeks) and we don’t know the long-term health effects. We might be currently making a recommendation that causes more harm than good.  
Before we can take-on a large clinical trial to study the effects of high salt intake on falls and heart attacks/stroke, we will start with a feasibility trial to find out whether we can recruit individuals with orthostatic hypotension, whether increases in salt intake are tolerable and get some pilot information on quality of life and blood pressure drops. The results of this trial will inform a larger clinical trial to assess the benefit of increased salt intake in people with orthostatic hypotension. 
  

12. Community-based exercise for older adults with chronic musculoskeletal pain: a randomised controlled feasibility trial 

Lead Applicant: Professor Karen McCreesh 
Host Institution: University of Limerick 
Study Type: Feasibility Study & SWAT 

Lay summary: Chronic pain affects one in three older Irish adults, and significantly negatively affects the person’s daily function and quality of life. The societal and healthcare costs of chronic pain have been estimated at €5.34 billion per year in Ireland. Physical activity is widely recommended to help manage chronic pain and improve overall health for older adults. However, that it is not always easy for older people with chronic pain to be active. Barriers to being active include fear of how safe it is, lack of skilled support, and a lack of exercise opportunities designed with the needs of people with chronic pain in mind. Community-based programmes which encourage physical activity in a local, supported manner could bridge this gap. In partnership with Chronic Pain Ireland and Limerick Sports Partnership, the research team will train community exercise trainers in the skills to support people with chronic pain to engage successfully in exercise. We will conduct a small-scale trial, randomising older adults with chronic pain to undertake either of two options: a community-based exercise programme, delivered by the newly educated trainers, or a control intervention where they will receive an education manual about physical activity for chronic pain. We are interested to know if the exercise programme is feasible, and acceptable, and will conduct interviews with the participants and trainers to receive their feedback on the study interventions. If this study shows that the programme is acceptable and feasible to deliver, it can then be tested in a larger scale trial in the future, to see if it is an effective and cost-effective method of supporting people with chronic pain. If deemed effective, the training and exercise classes can be easily rolled out nationwide through the network of County Sports Partnerships.