Rheumatoid Arthritis
Conditions
Brief summary
In this study investigators propose to address the following hypotheses: 1) Reduction in dietary sodium will decrease inflammation in patients with rheumatoid arthritis (RA). 2) Reduction in dietary sodium will decrease blood pressure in patients with RA. 3) Reduction in dietary sodium will decrease tissue sodium in patients with RA.
Detailed description
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.
Interventions
OTHERsalt
Participants will randomly eat a high salt diet for 8 weeks and a low salt diet for 8 weeks
Sponsors
Vanderbilt University Medical Center
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
DOUBLE (Investigator, Outcomes Assessor)
Masking description
Participants and nutrition staff will know when participants are on a high salt or low salt diet. Outcomes Assessor will be kept blinded. Participants will be told not to inform outcomes assessor what diet they are on.
Intervention model description
This will be a random-order, 2 period crossover study with washout
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORCharles M Stein, MBChB
Vanderbilt University Medical Center
Participant flow
Recruitment details
34 patients were screened for eligibility between January 2020 to June 2024 at Vanderbilt University Medical Center Rheumatology Clinic.
Pre-assignment details
18 of screened participants were randomized. Of the 16 not randomized, 15 did not meet inclusion criteria and 1 declined to participate.
Participants by arm
| Arm | Count |
|---|---|
| Sequence A: High Sodium Diet, Then Low Sodium Diet A high-sodium diet (200mmol/24hours) will be provided to participants for 8 weeks.
Then participants will have a 4-week washout in which they eat their typical diet.
Then a low sodium diet (50mmol/24hours) will be provided to participants for 8 weeks. | 9 |
| Sequence B: Low Sodium Diet, Then High Sodium Diet A low sodium diet (50mmol/24hours) will be provided to participants for 8 weeks.
Then participants will have a 4-week washout in which they eat their typical diet.
Then a high-sodium diet (200mmol/24hours) will be provided to participants for 8 weeks. | 8 |
| Total | 17 |
Baseline characteristics
| Characteristic | Sequence A: High Sodium Diet, Then Low Sodium Diet | Total | Sequence B: Low Sodium Diet, Then High Sodium Diet |
|---|---|---|---|
| Age, Continuous | 55 years | 55 years | 54 years |
| DAS28-CRP | 4.56 units on a scale | 4.56 units on a scale | 4.67 units on a scale |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 4 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 13 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 14 Participants | 5 Participants |
| Region of Enrollment United States | 9 participants | 17 participants | 8 participants |
| Sex: Female, Male Female | 8 Participants | 16 Participants | 8 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 0 Participants |
| Systolic blood pressure | 129 mmHg | 126 mmHg | 118 mmHg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 17 |
| other Total, other adverse events | 3 / 17 | 7 / 17 |
| serious Total, serious adverse events | 0 / 17 | 0 / 17 |
Outcome results
Primary
Change in Tissue Sodium
Investigators will measure change in tissue (skin) sodium using 3.0 T MRI equipped with a 23Na coil.
Time frame: 2 scans, one at end of week 8, and one at end of week 20
Population: Combined from Sequence A and B.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Sodium Diet | Change in Tissue Sodium | 17.1 mmol/L | Standard Deviation 5.1 |
| Low Sodium Diet | Change in Tissue Sodium | 16.7 mmol/L | Standard Deviation 8.2 |
p-value: 0.55Mixed Models Analysis
Secondary
Change in Blood Pressure
Investigators will measure change in systolic blood pressure.
Time frame: Measured at beginning and end of each diet period at weeks 0,8 and 12, 20
Population: Combined from Sequence A and B.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Sodium Diet | Change in Blood Pressure | 125 mmHg | Standard Deviation 10 |
| Low Sodium Diet | Change in Blood Pressure | 122 mmHg | Standard Deviation 10 |
| Low Sodium Diet Baseline | Change in Blood Pressure | 124 mmHg | Standard Deviation 14 |
| Low Sodium Diet After 8 Weeks | Change in Blood Pressure | 114 mmHg | Standard Deviation 11 |
p-value: 0.02Mixed Models Analysis
Secondary
Change in DAS28-CRP
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
Time frame: Measured at beginning and end of each diet period at weeks 0, 8, and 12, 20
Population: Combined from Sequence A and B.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Sodium Diet | Change in DAS28-CRP | 4.50 units on a scale | Standard Deviation 0.65 |
| Low Sodium Diet | Change in DAS28-CRP | 4.47 units on a scale | Standard Deviation 0.91 |
| Low Sodium Diet Baseline | Change in DAS28-CRP | 4.70 units on a scale | Standard Deviation 1.21 |
| Low Sodium Diet After 8 Weeks | Change in DAS28-CRP | 4.21 units on a scale | Standard Deviation 1.23 |
p-value: 0.76Mixed Models Analysis