ReDIRECT is the study acronym for Remote Diet Intervention to REduce long Covid symptoms Trial.
The aim of the ReDIRECT study is to test weight management as a strategy to improve and manage symptoms of Long COVID. There are several possible theories for the development of Long COVID following a COVID-19 infection, one of which includes a disruption of the immune system leading to greater levels of inflammation in the body. As weight loss is known to lower inflammatory levels, we are testing whether losing weight can help alleviate symptoms such as fatigue, breathlessness, and pain. However, weight loss can also benefit blood pressure, alleviate stress on kidneys, heart and lungs and may benefit people with Long COVID in several ways. Only by doing a trial can we test this out properly.
The study is funded by the National Institute of Health Research (NIHR), a UK government agency which funds research into health and social care.
Yes, and this study was also co-designed with people living with Long COVID, one of whom is a co-applicant. The trial was submitted to and reviewed by an NIHR panel comprising both people living with Long COVID and academics, and received funding against competition from other applications.
In the ReDIRECT study, we will be working closely with people with Long COVID to adapt and test a well-established weight management programme, which is delivered remotely with professional personal support to people at home. The weight management programme has been shown to be safe and effective in achieving and sustaining weight loss of over 10 kg and remission of type 2 diabetes for 46% of people after 1 year in a trial called DiRECT.
The Long COVID Research Priorities Report highlighted the need for “non-drug interventions” and “anti-inflammatory treatments” (weight loss being a proven anti-inflammatory intervention).
Strengths of the proposed intervention are that it:
People with Long COVID have been involved in this project throughout. We developed the research proposal with input from Long Covid Scotland, including a survey of members. Dr Tracy Ibbotson is our lead for PPI (Patient and Public Involvement) and two members of the team (Jane Ormerod and Chris White) live with Long COVID. The project proposal was reviewed by PPI members for the NIHR and an independent (third) patient representative sits on our Trial Steering Committee.
Patient involvement has shaped the project proposal by, for example, developing an innovative personalised primary outcome measure, whereby study participants nominate the Long COVID symptom that they would most like to see an improvement in, to be assessed as the main outcome.
ReDIRECT is one of 15 studies across the UK that have recently been funded by the National Institute for Health Research (NIHR). Other studies are looking at a range of different research areas that we hope will ultimately help improve everyone’s understanding of Long COVID and identify effective treatments and strategies to improve symptoms.
Our hypothesis is that weight reduction may help reduce symptoms for people living with Long COVID and higher weight.
Weight management programmes for other groups with chronic diseases have been able to reduce symptoms such as fatigue, breathlessness and pains, which are also common with Long COVID. However, we do not know how effective intentional weight loss is to reduce symptoms for people with Long COVID. The aim of this project is to test a well-established weight management programme, delivered and supported entirely remotely, in people with Long COVID.
Studies have shown strong links between higher weight and severity of COVID-19, exemplified by links to type 2 diabetes and hypertension, two conditions which are more common in people living with obesity. It follows therefore that excess weight may contribute to more adverse reactions with COVID-19 infection, and so to Long COVID.
Estimates vary, but around 10% of people infected with COVID-19 have symptoms for 12 weeks or longer (Long COVID) – that’s over a million people in the UK. While the only proven cause of Long COVID is contracting the COVID-19 virus, many people with Long COVID are living with higher weight and a high body mass index (BMI) has been associated with an increased risk of developing Long COVID.
The reasons for this are not well understood. It is likely that there are different underlying disease processes involved in different Long COVID symptoms. For instance, research has suggested the following potential contributors: persistent viral infection; small blood clots; and inflammation following initial infection. As a higher weight is a risk factor for more severe COVID-19 outcomes, it may enhance chances of people developing Long COVID.
ReDIRECT is testing whether supported weight loss, a potent non-pharmaceutical intervention that lessens inflammation levels and has other health benefits, can improve symptoms of Long COVID. We already know that weight management programmes for adults with higher weight can reduce symptoms such as fatigue, breathlessness and pains, which are also common with Long COVID. However, researchers do not know how effective intentional weight loss is to reduce these symptoms for overweight people with Long COVID. The best way to find out if an intervention is helpful or not is through a randomised controlled trial (RCT).
The ReDIRECT study is focusing on weight management, in response to the Long COVID Research Priorities Report highlighting the need for “non-drug interventions” and “anti-inflammatory treatments” (weight loss being a proven anti-inflammatory intervention). Only by doing a trial can we tell whether weight loss can help lessen Long COVID symptoms.
Weight loss trials will have most profound reductions in weight for those living with higher weight. If the results prove positive, further research could be undertaken with people with Long COVID and lower weight, but research usually starts with people with elevated risk factors, which is why we have designed the trial in this way.
The ReDIRECT study is a randomised controlled trial to evaluate a weight management programme, which means we will compare the effect of the programme on Long COVID symptoms against routine care.
The trial will be conducted with 200 people, identified through Long COVID patient and community groups. The 200 people will be randomly allocated to one of two groups: half of the participants will receive the personalised, professionally-supported weight management programme, while the other half continue to receive the care they currently receive. As well as receiving the free weight management programme, all participants will also receive a blood pressure machine and set of weighing scales to keep.
The goal of the study is to compare Long COVID symptoms, as well as changes in weight, quality of life, and value for money after 6 months. The control group will also receive the intervention, after a 6-month delay. The experiences of both groups will be documented for 12 months.
The programme will be delivered remotely, i.e. it can be followed from the comfort of your home. Another key feature of the trial is its focus on participant-selected key health outcomes, recognising the broad range of Long COVID symptoms.
All participants, regardless of group allocation, will be able to enter the weight management programme. We anticipate that participants in the study will lose weight, however there is no guarantee of improvement in your health or success of the intervention. Your participation in this study could lead us to a better understanding of whether weight loss can improve Long COVID symptoms, and in the long term, our study may benefit others living with Long COVID.
No – after you agree to participate, we will ask you to complete the baseline assessment after which you will be randomised to one of the two groups. If you are randomised to the treatment group, you will enter the supported weight management programme shortly after. If you are randomised to the control group, you will have access to the full programme 6 months following your group allocation.
No – the study is a randomised controlled trial, which means that you will be randomly allocated to one of the two groups. We have no control over which group you will be allocated to.
The weight management programme begins with meal replacements, using your choice of a range of porridge, soups and shakes, for 8-12 weeks to help you to lose weight quickly and easily. This is then followed by a stepped food reintroduction over 6 weeks and finally a food-based weight management period until the end of the study. You will be supported by registered dietitians throughout the entirety of the programme and also receive educational content (related to nutrition, activity and behaviour change strategies) to encourage healthy and sustainable behaviours.
No. There is no exercise or physical activity component to the ReDIRECT study. We recognise that many people with Long COVID experience debilitating fatigue and post-exertional malaise, so our trained dietitians will support pacing of daily activities, and also tailor any advice on activity to the individual participant.
The programme is patient-led. If participants want to have a break from using the meal replacements, they are supported by registered dietitians to do so.
The dietary intervention includes the use of meal replacements. These meal replacements are not FODMAP free, however that does not stop individuals who suffer from IBS using meal replacements and people with IBS have accessed the weight management programme before. While most have tolerated the meal replacements, your tolerance to the programme would have to be assessed after you join the programme.
The programme is provided by registered dietitians who will work with individuals to aid tolerance to meal replacements. During the Food Reintroduction phase of the programme, the programme is tailored to the individual needs of the participants, and adapted to manage symptoms of IBS.
The dietary intervention includes the use of meal replacements. All flavours are suitable for a vegetarian diet. There are two flavours (cappuccino and leek & potato soup) which are suitable for people following a vegan diet.
We will use an innovative approach to personalisation, with each participant selecting their main symptom as primary outcome. We have developed detailed questionnaires to collect this information.
Some patients with Long Covid have reported a worsening of symptoms such as pain and gastrointestinal upset related to eating. The distinction between the effect of weight loss and the effect of eating less will hopefully become clearer during the food reintroduction phase. We will also be conducting in-depth qualitative interviews with a sample of participants, during which they will be able to discuss changes in symptoms in more detail.
To assess any potential effect the intervention may have on Long COVID symptoms, we will compare two groups of people who live with Long COVID. For the first six months of the study, one group will receive the weight management programme (‘treatment’ group), while the other will continue to receive their usual care (‘control’ group). If a natural change in Long COVID symptoms occurs in this time (an improvement or worsening), we expect these changes to happen similarly in both groups. The comparison of the groups allows us to identify any additional effect the weight management programme may have.