Dietary Salt in Rheumatoid Arthritis

The study is a random-order, 2 period crossover study with washout. Participants will be randomly assigned to be on the high-sodium diet (200mmol/24hours x 8weeks) or low-sodium diet (50mmol/24hours x 8 weeks ) with crossover separated by 4-week washout period. Investigators will allow a 7-day window on the diet (i.e., to facilitate scheduling the diet can be between 7-9 weeks), and investigators will allow a 1-week window for the washout (i.e., washout can be 3-5 weeks).

Investigators will measure changes in inflammation (as measured by DAS28 (using tender and swollen joint count, disease activity and sedimentation rate)), blood pressure measured over a 24 hour period, and tissue sodium (using Magnetic Resonance Imaging (MRI)).

If a relatively simple dietary modification has a clinically important effect on inflammation and blood pressure regulation in vivo in patients with RA, this will have far-reaching implications for the treatment of RA and prevention of Cardiovascular disease in this population.

• salt (Other): Participants will randomly eat a high salt diet for 8 weeks and a low salt diet for 8 weeks

Primary outcomes

• Change in Tissue Sodium [2 scans, one at end of week 8, and one at end of week 20]: Investigators will measure change in tissue (skin) sodium using 3.0 T MRI equipped with a 23Na coil.

Secondary outcomes

• Change in DAS28-CRP [Measured at beginning and end of each diet period at weeks 0, 8, and 12, 20]: DAS28-CRP score is a disease activity score based on 28 joints and C-reactive protein. Lower is better. Range= 0.96 units to 10. DAS28-CRP = 0.56 x sqrt(tender joint count) + 0.28 x sqrt(swollen joint count) + 0.36 x ln(C-reactive protein + 1) + 0.014 x global health score + 0.96
• Change in Blood Pressure [Measured at beginning and end of each diet period at weeks 0,8 and 12, 20]: Investigators will measure change in systolic blood pressure.

Sex: All, ages: 18 Years to 80 Years

Inclusion Criteria:

1. Male and female patients older than 18 years who are willing to participate.
2. Satisfy the ACR criteria for the diagnosis of RA.
3. Have stable disease activity as evidenced by no clinically meaningful change in immunomodulating or corticosteroid therapy in the past 1 month.
4. Have moderate disease activity as reflected by a minimum of 3 swollen and tender joints.

Exclusion Criteria:

1. Pregnancy
2. Receiving dialysis
3. Organ or bone marrow transplant
4. Taking diuretics, uncontrolled hypertension (>160/100 mmHg), or cardiac failure requiring treatment.
5. Severe edema (as judged by the investigator)
6. Diabetes mellitus treated with an insulin pump
7. Major surgery within the previous 3 months
8. Severe co-morbid conditions such as active cancer likely to compromise study participation
9. Unwillingness, or other inability, to cooperate
10. Contraindication to MRI
11. Presence of a condition that could make 24-hour blood pressure monitoring difficult: atrial fibrillation, inability to operate machine, receiving anticoagulants, presence of a condition that in the opinion of the investigator may be exacerbated by blood pressure cuff inflation (e.g., lymphedema).

Participant flow

Outcome results

• Change in Tissue Sodium (Primary), Mean, mmol/L: High Sodium Diet 17.1 +/- 5.1; Low Sodium Diet 16.7 +/- 8.2 (p 0.55)
• Change in DAS28-CRP (Secondary), Mean, units on a scale: High Sodium Diet Baseline 4.50 +/- 0.65; High Sodium Diet After 8 Weeks 4.47 +/- 0.91; Low Sodium Diet Baseline 4.70 +/- 1.21; Low Sodium Diet After 8 Weeks 4.21 +/- 1.23 (p 0.31)
• Change in Blood Pressure (Secondary), Mean, mmHg: High Sodium Diet Baseline 125 +/- 10; High Sodium Diet After 8 Weeks 122 +/- 10; Low Sodium Diet Baseline 124 +/- 14; Low Sodium Diet After 8 Weeks 114 +/- 11 (p 0.02)

Adverse events

Time frame: 20 weeks

Other adverse events by term

Limitations and caveats: Enrollment was impeded by COVID19.

• Study Protocol and Statistical Analysis Plan (PDF, 2023-03-30)
• Informed Consent Form (PDF, 2023-12-07)

• Charles M Stein, MBChB, Principal investigator, Vanderbilt University Medical Center

NIH grants: R01HL140145