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

Study Overview
=================
Brief Summary
-----------------
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.

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

Conditions
-----------------
Obesity, Lupus Erythematosus

Intervention / Treatment
-----------------
* Dietary Supplement: Vitamin B12 + folic acid supplementation
* Dietary Supplement: Placebo supplementation


Participation Criteria
=================
Eligibility Criteria
-----------------
- Female Inclusion criteria: In pre-menopausal period Aged between 18 to 40 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 glucocorticoid treatment at a dosage <10 mg/day Under treatment with chloroquine at a stable dose Exclusion Criteria: Infection Diabetes Smokers Pregnancy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Supplemented Lean Group<br> | Dietary Supplement: Vitamin B12 + folic acid supplementation<br>* 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.<br>|
| Experimental: Supplemented Obese Group<br> | Dietary Supplement: Vitamin B12 + folic acid supplementation<br>* 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.<br>|
| Placebo Comparator: Control Lean Group<br> | Dietary Supplement: Placebo supplementation<br>* 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.<br>|
| Placebo Comparator: Control Obese Group<br> | Dietary Supplement: Placebo supplementation<br>* 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.<br>|

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 DNMT3 gene expression at 12 weeks | Relative gene expression of DNMT3 | 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 global DNA hydroxymethylation at 12 weeks | Percentage of global DNA hydroxymethylation level | 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 dietary intake at 12 weeks |  | 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 |