Clinical trial NCT06831331: Nutrition in Rheumatoid Arthritis
Official title: NUTRA- Nutrition in Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Rheumatoid Arthritis (RA)
Keywords: nutrition
diet
nordic nutrition recommendations
inflammation
metabolomics
cardiovascular risk factors
Lead sponsor: Vastra Gotaland Region
Sponsor class: OTHER_GOV
Collaborators: name: Göteborg University
First posted: 2025-02-18
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Background: Individuals with Rheumatoid Arthritis (RA) often experience persistent symptoms such as pain and stiffness despite modern pharmacological treatments. They also have an increased risk of cardiovascular disease. Elevated risk factors for cardiovascular disease limit the options for symptom-relieving medications, making a reduction in these risk factors highly desirable. Diet has been shown to reduce several of these factors, but the scientific evidence for rheumatoid arthritis is limited, and thus tailored dietary advice is lacking.

Objective: The purpose of the NUTRA study is to evaluate the effect of a diet that follows the updated Nordic Nutrition Recommendations (2023) on disease activity and cardiovascular risk factors in individuals with newly diagnosed RA. Specifically, the study will analyze the impact of the diet on clinically relevant markers such as blood pressure, lipid profile, inflammatory markers, and body composition.

Study Plan: The study will include about 150 patients, and participants will follow a standardized care protocol where, at their three-month visit, they are randomized into either a diet following the Nordic Nutrition recommendations or a Nutrient rich diet. The intervention diets, will be added as a complementary treatment to the medications the patients are already taking. Participants will receive menus, recipes and some foods for three months, followed by self-maintenance of the diet. Clinical markers will be evaluated before the intervention as well as at three and nine months. Artificial intelligence will be used to predict which factors are crucial for achieving the best possible outcomes from dietary treatment.

Significance: The NUTRA study is highly significant as it aims to generate evidence to guide the design of dietary interventions for patients with rheumatoid arthritis. By understanding the potential role of diet in reducing both disease activity and cardiovascular risk, the study may contribute to improved treatment strategies for this challenging patient group.

Detailed description: Study Design and Methodology for NUTRA The NUTRA-trial is a 3-month randomized, controlled, parallel dietary intervention trial. It will compare a personalized healthy diet intervention following the updated Nordic Nutrition Recommendations 2023 to a nutrient rich diet. The Nordic Nutrition Recommendations is evidence based recommendations with focus to limit the dietary risks associated to the burden of disease (specifically ischemic heart disease, type 2 diabetes, stroke and colon and rectum cancers) in the Nordic countries.

Study participants and recruitment: Patients diagnosed with RA in the Gothenburg region and additional sites in Sweden will be recruited for three years. All patients that are diagnosed with RA are "labelled" with "care process RA" in the Healthcare Information Systems (HIS) (for example ELVIS in Region Vastra Gotaland) of Sweden. The investigators will select and invite all patients coded with RA diagnosis by letter within three months from diagnosis. The investigators expect to recruit about 110-150 men and women, likely resulting in about 100-120 participants completing the dietary intervention period and 100 participants the 1 year (i.e. six months after dietary intervention) follow up. Additional sites will be added to increase the recruitment pace if needed. The recruitment pace, compliance, study setup and budget will be evaluated after recruitment and completion of the first 3 months of the study for the first ten participants (during 2025).

Standard care pharmacological treatment: According to the course of medical care most patients diagnosed with RA will start on the first-line treatment (Methotrexate and/or cortisone) immediately after diagnosis. At the three-month clinic visit treatment is evaluated and most patients continue Methotrexate, and some will be offered additional biological treatment. Participants continuing Methotrexate and/or additional biological treatment will be invited to continue in NUTRA-trial.

Data and sample collection: Patients with RA follow a course of medical care. Study baseline (visit 1) will be jointly with the three-month clinical visit, visit 2 with the six-month clinical visit and visit 3 with the 12-month clinical visit. Data will be collected from the clinical visits. In addition, visits before (visit 1) and after (visit 2) the intervention period will include blood and urine collection, clinical phenotype, blood pressure, a 4-day weighed dietary dairy, joint examination, questionnaires (SF-36, HAQ) and physical activity (activity/fitness tracker during the whole period). Visit 1 will also include study information, informed consent, randomization, and a food frequency questionnaire. Patients will be followed up six months after intervention (visit 3) to evaluate if dietary changes persist and for CVD risk factors including lipid patterns.

Assignment: Participants will be randomized (1:1) to either Nordic Nutrition recommendation or Nutrient rich diet intervention at the baseline visit (3 months post diagnosis, visit 1). Randomization will be stratified for site, sex, BMI, and diagnosis (seropositive or negative including both rheumatoid factor (RF) and anticitrullinated protein antibody (ACPA)). To reduce risk of bias, cut-offs for age, diagnosis and block size will be unknown to study personnel that select patients coded with "care process RA" from the system. In addition, block size will be of different sizes, so that risk for allocation bias will be maximally reduced.

Nutrition recommendation: Participants will receive a startup grocery bag and be encouraged to follow the Nordic Recommendations 2023. In addition, a dietitian will provide personalized dietary advice based on the 4-day dietary diary, to improve compliance and to ensure that the participants reach dietary goals.

Nutrient rich diet: Participants will receive a startup grocery bag and be encouraged to consume nutrient rich foods with high protein quality such as meat, dairy and egg, but without menus to support this intake. They will be offered personalized dietary advice after the 12-month clinical visit.

Both groups will wear activity/fitness devices during the intervention period to measure physical activity and will be encouraged to lose weight if overweight. All will also get some general advice regarding a healthy diet, physical activity, and weight within the ordinary care.

Eligibility criteria: Inclusion Criteria:

* newly diagnosed RA (within 3 months) that have started on Methotrexate and/or cortisone treatment. RA is defined according to the criteria from EULAR/American College of Rheumatology (ACR) 2010.
* BMI 18.5-40 kg/m2
* willing to follow the intervention diet

Exclusion Criteria:

* pregnancy
* lactation
* diagnosis for cancer or other life-threatening diseases
* diabetes type 1 and 2
* inflammatory bowel disease or celiac disease

Primary outcomes:
measure: Patterns of serum inflammatory markers
timeFrame: 3 months dietary intervention
Secondary outcomes:
measure: Remission yes/no
timeFrame: 3 months dietary intervention and at 9 months follow up
measure: Disease activity DAS28-CRP
timeFrame: 3 months dietary intervention and at 9 months follow up
measure: Apolipoprotein B100
timeFrame: 3 months dietary intervention and at 9 months follow up
measure: triacylglycerides
timeFrame: 3 months dietary intervention and at 9 months follow up
measure: high density lipoprotein
timeFrame: 3 months dietary intervention and at 9 months follow up
measure: Low density lipoprotein (LDL)
timeFrame: 3 months dietary intervention and at 9 months follow up
measure: total cholesterol
timeFrame: 3 months dietary intervention and at 9 months follow up
measure: Erythrocyte sediment rate (ESR)
timeFrame: 3 months dietary intervention and at 9 months follow up
measure: high sensitive-C-reactive protein (hs-CRP)
timeFrame: 3 months dietary intervention and at 9 months follow up
measure: Corticosteroid use
timeFrame: 3 months dietary intervention and at 9 months follow up
measure: Physical disability
timeFrame: 3 months dietary intervention and at 9 months follow up
measure: Quality of life (RAND-SF36)
timeFrame: 3 months dietary intervention and at 9 months follow up
measure: Disease activity score DAS28-ESR
timeFrame: 3 months dietary intervention and at 9 months follow up
Other outcomes:
measure: Body mass index (BMI)
timeFrame: 3 months dietary intervention and at 9 months follow up
measure: Body composition
timeFrame: 9 months follow up
measure: Patterns of metabolites
timeFrame: 3 months dietary intervention
measure: European League Against Rheumatism (EULAR) criteria for disease activity
timeFrame: 3 months dietary intervention and at 9 months follow up
measure: Differences in changes in fatty acid patterns in plasma
timeFrame: 3 months dietary intervention
measure: Differences in changes in fatty acid patterns in erythrocytes
timeFrame: 3 months dietary intervention
Locations:
city: Gothenburg
country: Sweden
facility: Klinisk Reumatologiskt Forskningscentrum, Sahlgrenska University Hospital
Study officials:
References: