Methyl-donor Nutrient Supplementation and Methylation Profile in Lupus Patients With Obesity

Effect of Methyl-donor Nutrient Supplementation on Methylation Profile of Inflammatory-related Genes in Lupus Patients With Obesity: a Clinical Trial

Dietary supplementation with methyl donors has been demonstrated to increase DNA methylation in leucocytes whereas a limited dietary intake of methyl donors was associated with DNA hypomethylation. Considering SLE disease, previously study showed that high doses of vitamin B6 and folate were associated with less severe SLE. Furthermore, some evidences reported a relatively high incidence of decreased serum B12 levels in rheumatic patients. This led to the suggestion that diets rich in methyl group donors could have beneficial effects on SLE.

Study Overview

• Status: Enrolling by invitation
• Conditions: Overweight and Obesity; Lupus Erythematosus
• Intervention / Treatment: Dietary supplement: Vitamin B12 + folic acid supplementation; Dietary supplement: Placebo supplementation

• Study Type: Interventional
• Enrollment (Estimated): 51
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • Sao Paulo, Brazil, 05508-030
    • Univsersity of Sao Paulo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

• SLE diagnosis
• Female
• In pre-menopausal period
• Aged between 18 to 45 years
• Patients that meet the classification criteria according to Systemic Lupus International Collaborating Clinics classification criteria (SLICC)
• Patients with SLEDAI score ≤ 4 on Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K)
• Under prednisone treatment at a dosage <10 mg/day
• Under treatment with chloroquine at a stable dose
• BMI > 18,5 kg/m2

Exclusion Criteria:

• Current infection
• Diabetes
• Arterial hypertension
• Smokers
• Pregnancy
• Anticoagulants use
• Methotrexate use
• Other autoimmune diseases
• Current vitamin B12 or/and folic acid supplementation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Supplemented Normal Weight Group; Patients with normal weight (BMI between 18.5 and 24.9 kg/m²) that will receive supplementation.	Dietary supplement: Vitamin B12 + folic acid supplementation; A 12 weeks parallel-group randomised controlled trial will be performed, in which erythematous lupus patients will complete a vitamin B12 and folic acid supplementation, in addition to the usual therapy. The dietary supplementation will be by capsules, which will content 400 mcg of folic acid and 2000 mcg of vitamin B12 each.
Experimental: Supplemented Excess Body Weight Group; Patients with excess body weight (BMI > 25 kg/m²) that will receive supplementation.	Dietary supplement: Vitamin B12 + folic acid supplementation; A 12 weeks parallel-group randomised controlled trial will be performed, in which erythematous lupus patients will complete a vitamin B12 and folic acid supplementation, in addition to the usual therapy. The dietary supplementation will be by capsules, which will content 400 mcg of folic acid and 2000 mcg of vitamin B12 each.
Placebo Comparator: Control Normal Weight Group; Patients with normal weight (BMI between 18.5 and 24.9 kg/m²) that will receive placebo.	Dietary supplement: Placebo supplementation; A 12 weeks parallel-group randomised controlled trial will be performed, in which erythematous lupus patients will complete a placebo supplementation.The placebo and vitamin B12 + folic acid supplement will be indistinguishable in terms of taste, smell, and appearance.
Placebo Comparator: Control Excess Body Weight Group; Patients with excess body weight (BMI > 25 kg/m²) that will receive placebo.	Dietary supplement: Placebo supplementation; A 12 weeks parallel-group randomised controlled trial will be performed, in which erythematous lupus patients will complete a placebo supplementation.The placebo and vitamin B12 + folic acid supplement will be indistinguishable in terms of taste, smell, and appearance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline on DNA methylation profile at 12 weeks	Percentage of DNA methylation level	Baseline and 12 weeks
Change from baseline on weight at 12 weeks	Weight in kilograms	Baseline and 12 weeks
Change from baseline on serum vitamin B12 concentrations at 12 weeks	Serum vitamin B12 concentrations in pg/mL	Baseline and 12 weeks
Change from baseline on serum folic acid concentrations at 12 weeks	Serum folic acid concentrations in ng/mL	Baseline and 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Age of onset	Units of Measure: years	Baseline
Duration of disease since diagnosis	Units of Measure: years	Baseline
Change from baseline on miR-146 expression at 12 weeks	Relative miR-146 expression	Baseline and 12 weeks
Change from baseline on miR-181 expression at 12 weeks	Relative miR-181 expression	Baseline and 12 weeks
Change from baseline on miR-21 expression at 12 weeks	Relative miR-21 expression	Baseline and 12 weeks
Change from baseline on miR-126 expression at 12 weeks	Relative miR-126 expression	Baseline and 12 weeks
Change from baseline on DNMT1 gene expression at 12 weeks	Relative gene expression of DNMT1	Baseline and 12 weeks
Change from baseline on serum leptin concentrations at 12 weeks	Serum leptin concentration in ng/mL	Baseline and 12 weeks
Change from baseline on serum C-reactive protein concentrations at 12 weeks	Serum C-reactive protein concentration in ng/mL	Baseline and 12 weeks
Change from baseline on serum adipokines concentrations at 12 weeks	Serum adipokines concentration in ng/mL	Baseline and 12 weeks
Change from baseline on serum triglycerides concentrations at 12 weeks	Serum triglycerides concentration in mg/dL	Baseline and 12 weeks
Change from baseline on serum cholesterol concentrations at 12 weeks	Serum cholesterol concentrations in mg/dL	Baseline and 12 weeks
Change from baseline on serum glucose concentrations at 12 weeks	Serum glucose concentrations in mg/dL	Baseline and 12 weeks
Change from baseline on abdominal circumference at 12 weeks	Abdominal circumference in centimeters	Baseline and 12 weeks
Change from baseline on fat mass at 12 weeks	Fat mass in kilograms	Baseline and 12 weeks
Change from baseline on body mass index at 12 weeks	Body mass index in kilograms/meters^2	Baseline and 12 weeks
Change from baseline on height at 12 weeks	Height in meters	Baseline and 12 weeks
Change from baseline on TNF-a gene expression at 12 weeks	Relative gene expression of TNF-a	Baseline and 12 weeks
Change from baseline on LEP gene expression at 12 weeks	Relative gene expression of LEP	Baseline and 12 weeks
Change from baseline on ADIPOQ gene expression at 12 weeks	Relative gene expression of ADIPOQ	Baseline and 12 weeks
Change from baseline on MTHFR gene expression at 12 weeks	Relative gene expression of MTHFR	Baseline and 12 weeks
Change from baseline on STAT3 gene expression at 12 weeks	Relative gene expression of STAT3	Baseline and 12 weeks
Change from baseline on IL-6 gene expression at 12 weeks	Relative gene expression of IL-6	Baseline and 12 weeks
Change from baseline on serum IL-6 concentrations at 12 weeks	Serum IL-6 concentration in ng/mL	Baseline and 12 weeks
Change from baseline on serum IL-17 concentrations at 12 weeks	Serum IL-17 concentration in ng/mL	Baseline and 12 weeks
Change from baseline on serum IL-2 concentrations at 12 weeks	Serum IL-2 concentration in ng/mL	Baseline and 12 weeks
Change from baseline on serum TNF-a concentrations at 12 weeks	Serum TNF-a concentration in ng/mL	Baseline and 12 weeks
Change from baseline on dietary intake at 12 weeks	Dietary intake in g and percentage	Baseline and 12 weeks
Change from baseline on fat free mass at 12 weeks	Fat free mass in kilograms	Baseline and 12 weeks

Collaborators and Investigators

• Sponsor: University of Sao Paulo

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Actual): July 31, 2022
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: August 10, 2021
• First Submitted That Met QC Criteria: October 15, 2021
• First Posted (Actual): October 28, 2021

Study Record Updates

• Last Update Posted (Estimated): May 2, 2024
• Last Update Submitted That Met QC Criteria: April 30, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Body Weight; Obesity; Overweight; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Hematinics; Folic Acid; Vitamin B 12; Hydroxocobalamin
• Other Study ID Numbers: SLE and DNA methylation

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No