Effectiveness of Therapeutic Fasting and Specific Diet in Patients With Rheumatoid Arthritis: a Randomized Controlled Clinical Trial

Brief Summary

Detailed Description

Rheumatoid arthritis is an inflammatory-destructive joint disease for which up to date etiopathogenetical causes are lacking. In recent years, numerous new therapeutic concepts have been developed in the form of targeted antibody therapies that can block various inflammatory mechanisms. Although better treatment successes in comparison with conventional therapies were achieved, patients respond to the new therapies in very different ways. As a result the optimal drug needs to be identified for each patient through individual treatment trials. So far, no healings have been achieved and the progression of the disease can be stopped only by permanent suppression of the inflammatory response. In addition to different immunological mechanisms and genetic predispositions, interactions with the microbiome of the intestine are increasingly being discussed in recent years. A dysbiotic intestinal flora, characterized by the loss of beneficial bacteria and a concomitant increase in potentially pathogenic microbes, is associated with chronic inflammatory syndromes. Modified fasting (up to 500 kcal energy intake per day) for 7-10 days leads to an improvement of the symptoms in many patients with rheumatoid arthritis and is regularly used by the applicants for the treatment of rheumatoid arthritis. Several clinical studies have shown that therapeutic fasting produces anti-inflammatory effects. However, so far no standardized method for long-term stabilization of corresponding effects after resumption of nutrition has been established. Recent transcriptome analyzes have not only revealed numerous new potential markers, but also increasingly allow conclusions to be drawn from these extensive datasets that suggest immunological relationships between specific genes. In preliminary studies within the framework of a project of the same study group, it was possible to identify inflammatory profiles of individual foods and to identify molecular markers of disease activity in rheumatoid arthritis whose diagnostic value has been tested and interpreted under the influence of fasting. These markers will now be clinically evaluated in this study in collaboration with both centers. The hypothesis is that a combination of fasting and subsequent diagnosis-specific diet change will improve the rheumatic symptoms. In this context, it will also be analyzed, which meaning of the changes 1) of the metabolism and 2) of the microbiome, mediated by fasting and nutrition, belongs. This will be demonstrated by using already identified markers for genotypic traits, gene expression traits, characteristics of protein expression, protein activities, and antigen-specific immunological response patterns. The present research project aims to combine the different aspects of a possible anti-rheumatic nutrition and to evaluate the nutritherapeutic concept in an RCT. We suggest that a part of the anti-inflammatory effects of fasting and best practice diets may be due to a change in the composition of the intestinal flora mediated. Thus this study contributes to the extended therapy of rheumatoid arthritis.

Primary Outcomes

Secondary Outcomes

• Rheumatoid factor (IgM)(Date of inclusion (baseline))
• American College of Rheumatology (ACR) response criteria(Date of inclusion (baseline), day 7, after 6 and 12 weeks)
• Bio-electrical impedance analysis (BIA)(Date of inclusion (baseline), after 6 and 12 weeks)
• Creatinine in µmol per liter (µmol/L)(Date of inclusion (baseline), day 7, after 6 and 12 weeks)
• Abdominal circumference(Date of inclusion (baseline), after 6 and 12 weeks)
• Disease Activity Score 28 (DAS-28-CRP)(Date of inclusion (baseline), day 7, after 6 and 12 weeks)
• Simplified Disease Activity Index Score (SDAI)(Date of inclusion (baseline), day 7, after 6 and 12 weeks)
• Hepatic transaminases (GPT, GOT) and Gamma glutamyl transpeptidase (y-GT)(Date of inclusion (baseline), day 7, after 6 and 12 weeks)
• Estimated glomerular filtration rate (eGFR) in milliliter per minute (mL/min)(Date of inclusion (baseline), day 7, after 6 and 12 weeks)
• Electrolytes(Date of inclusion (baseline), day 7, after 6 and 12 weeks)
• Creatine kinase (U/L)(Date of inclusion (baseline), day 7, after 6 and 12 weeks)
• CRP in milligram per liter (mg/L)(Date of inclusion (baseline), day 7, after 6 and 12 weeks)
• Blood lipids and fasting glucose(Date of inclusion (baseline), day 7, after 6 and 12 weeks)
• Resting blood pressure(Date of inclusion (baseline), after 6 and 12 weeks)
• Differential blood count(Date of inclusion (baseline), day 7, after 6 and 12 weeks)
• Total protein in grams per liter (g/L)(Date of inclusion (baseline), day 7, after 6 and 12 weeks)
• International normalized ratio (INR)(Date of inclusion (baseline), day 7, after 6 and 12 weeks)
• Lactate dehydrogenase (LDH) (U/L)(Date of inclusion (baseline), day 7, after 6 and 12 weeks)
• Uric acid (µmol/L)(Date of inclusion (baseline), day 7, after 6 and 12 weeks)
• Food selection(Date of inclusion (baseline), after 4 and 9 weeks)
• Pulse rate(Date of inclusion (baseline), after 6 and 12 weeks)
• Erythrocyte sedimentation rate (ESR) in millimeters per hour (mm/h)(Date of inclusion (baseline), day 7, after 6 and 12 weeks)
• Partial thromboplastin time (PTT) in seconds (s)(Date of inclusion (baseline), day 7, after 6 and 12 weeks)
• Phenotyping of immune cells(Date of inclusion (baseline), day 7, after 6 and 12 weeks)
• Anti-cyclic citrullinated peptide (anti-CCP)(Date of inclusion (baseline), day 7, after 6 and 12 weeks)
• Analgetics intake(Up to 12 weeks)
• Mood questionnaire (Profile of Mood States, POMS)(Date of inclusion (baseline), after 6 and 12 weeks, after 6 months)
• Metabolic plasma metabolites(Date of inclusion (baseline), day 7, after 6 and 12 weeks)
• Quantification of Behavioral Factors(Date of inclusion (baseline), after 6 and 12 weeks)
• Gut microbiome(Date of inclusion (baseline), day 7, week 6 and week 12)
• Dietary Behaviour(Date of inclusion (baseline), after 6 and 12 weeks)
• Urine analysis (10 ml midstream urine)(Date of inclusion (baseline), day 7, after 6 and 12 weeks)
• The Hannover Functional Ability Questionnaire (Funktionsfragebogen Hannover, FFbH-R)(Date of inclusion (baseline), after 6 and 12 weeks, after 6 months)
• Quality of Life questionnaire (WHO-5)(Date of inclusion (baseline), after 6 and 12 weeks, after 6 months)
• Documentation of Behavioral Factors(Up to 12 weeks)
• Sociodemographic Measurements(Date of inclusion (baseline))
• Medication intake(Date of inclusion (baseline), after 6 and 12 weeks)
• Stress questionnaire (Cohen Perceived Stress Scale, CPSS)(Date of inclusion (baseline), after 6 and 12 weeks, after 6 months)