Clinical trial NCT03856190: Effectiveness of Therapeutic Fasting and Specific Diet in Patients With Rheumatoid Arthritis
Official title: Effectiveness of Therapeutic Fasting and Specific Diet in Patients With Rheumatoid Arthritis: a Randomized Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Rheumatoid Arthritis
Keywords: Fasting
Vegan
Plant based
Randomized Trial
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: Braunschweig Integrated Centre of Systems Biology (BRICS), Germany
name: University of Luxembourg
First posted: 2019-02-27
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: The aim of this trial is an evaluation of the effectiveness of fasting and a subsequent diagnosis-specific diet change in patients with rheumatoid arthritis in respect to improving rheumatic symptoms and further to investigate possible mechanisms of this improvement.

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.

Eligibility criteria: Inclusion Criteria:

1. Rheumatoid arthritis
2. free of any serious medical condition that precludes safe participation in an exercise program, such as coronary artery disease, severe hypertension, peripheral vascular disease, stroke, congestive heart failure, chronic obstructive pulmonary disease, insulin-dependent diabetes, psychiatric disease, renal disease, liver disease, active cancer other than skin cancer, and anemia
3. Ability to understand the intervention concept and written consent to participate;
4. Willingness to accept randomization and undergo the testing and intervention procedures and deliver stool, blood and urine samples for testing
5. Age 18-70 years (inclusive)
6. drug therapy was not started in the last 8 weeks before screening

Exclusion Criteria:

1. Gout or septic arthritis
2. Psychiatric disease that interferes with the understanding and implementation of the intervention
3. Pregnancy or breast feeding
4. In the case of pronounced anemia (Hb \<10 mg / dl) no inclusion in the examination or no additional blood sampling is carried out
5. Underweight (BMI \<18,5) or weight loss of \>3kg/5kg in the last/last 3 month(s)
6. Eating disorder (such as bulimia, anorexia nervosa) in the last 5 years
7. Current vegan nutrition
8. Non-existence of email address or internet access

Primary outcomes:
measure: Health Assessement Questionnaire (HAQ)
timeFrame: Date of inclusion (baseline), day 7, after 6 and 12 weeks
Secondary outcomes:
measure: Disease Activity Score 28 (DAS-28-CRP)
timeFrame: Date of inclusion (baseline), day 7, after 6 and 12 weeks
measure: American College of Rheumatology (ACR) response criteria
timeFrame: Date of inclusion (baseline), day 7, after 6 and 12 weeks
measure: Simplified Disease Activity Index Score (SDAI)
timeFrame: Date of inclusion (baseline), day 7, after 6 and 12 weeks
measure: Bio-electrical impedance analysis (BIA)
timeFrame: Date of inclusion (baseline), after 6 and 12 weeks
measure: Bio-electrical impedance analysis (BIA)
timeFrame: Date of inclusion (baseline), after 6 and 12 weeks
measure: Abdominal circumference
timeFrame: Date of inclusion (baseline), after 6 and 12 weeks
measure: Resting blood pressure
timeFrame: Date of inclusion (baseline), after 6 and 12 weeks
measure: Pulse rate
timeFrame: Date of inclusion (baseline), after 6 and 12 weeks
measure: Differential blood count
timeFrame: Date of inclusion (baseline), day 7, after 6 and 12 weeks
measure: Hepatic transaminases (GPT, GOT) and Gamma glutamyl transpeptidase (y-GT)
timeFrame: Date of inclusion (baseline), day 7, after 6 and 12 weeks
measure: Total protein in grams per liter (g/L)
timeFrame: Date of inclusion (baseline), day 7, after 6 and 12 weeks
measure: Creatinine in µmol per liter (µmol/L)
timeFrame: Date of inclusion (baseline), day 7, after 6 and 12 weeks
measure: Creatine kinase (U/L)
timeFrame: Date of inclusion (baseline), day 7, after 6 and 12 weeks
measure: Estimated glomerular filtration rate (eGFR) in milliliter per minute (mL/min)
timeFrame: Date of inclusion (baseline), day 7, after 6 and 12 weeks
measure: Electrolytes
timeFrame: Date of inclusion (baseline), day 7, after 6 and 12 weeks
measure: Erythrocyte sedimentation rate (ESR) in millimeters per hour (mm/h)
timeFrame: Date of inclusion (baseline), day 7, after 6 and 12 weeks
measure: CRP in milligram per liter (mg/L)
timeFrame: Date of inclusion (baseline), day 7, after 6 and 12 weeks
measure: International normalized ratio (INR)
timeFrame: Date of inclusion (baseline), day 7, after 6 and 12 weeks
measure: Partial thromboplastin time (PTT) in seconds (s)
timeFrame: Date of inclusion (baseline), day 7, after 6 and 12 weeks
measure: Lactate dehydrogenase (LDH) (U/L)
timeFrame: Date of inclusion (baseline), day 7, after 6 and 12 weeks
measure: Blood lipids and fasting glucose
timeFrame: Date of inclusion (baseline), day 7, after 6 and 12 weeks
measure: Uric acid (µmol/L)
timeFrame: Date of inclusion (baseline), day 7, after 6 and 12 weeks
measure: Rheumatoid factor (IgM)
timeFrame: Date of inclusion (baseline)
measure: Anti-cyclic citrullinated peptide (anti-CCP)
timeFrame: Date of inclusion (baseline), day 7, after 6 and 12 weeks
measure: Phenotyping of immune cells
timeFrame: Date of inclusion (baseline), day 7, after 6 and 12 weeks
measure: Metabolic plasma metabolites
timeFrame: Date of inclusion (baseline), day 7, after 6 and 12 weeks
measure: Urine analysis (10 ml midstream urine)
timeFrame: Date of inclusion (baseline), day 7, after 6 and 12 weeks
measure: Gut microbiome
timeFrame: Date of inclusion (baseline), day 7, week 6 and week 12
measure: Sociodemographic Measurements
timeFrame: Date of inclusion (baseline)
measure: Medication intake
timeFrame: Date of inclusion (baseline), after 6 and 12 weeks
measure: Analgetics intake
timeFrame: Up to 12 weeks
measure: Documentation of Behavioral Factors
timeFrame: Up to 12 weeks
measure: Quantification of Behavioral Factors
timeFrame: Up to 12 weeks
measure: Quantification of Behavioral Factors
timeFrame: Date of inclusion (baseline), after 6 and 12 weeks
measure: Food selection
timeFrame: Date of inclusion (baseline), after 4 and 9 weeks
measure: Dietary Behaviour
timeFrame: Date of inclusion (baseline), after 6 and 12 weeks
measure: The Hannover Functional Ability Questionnaire (Funktionsfragebogen Hannover, FFbH-R)
timeFrame: Date of inclusion (baseline), after 6 and 12 weeks, after 6 months
measure: Mood questionnaire (Profile of Mood States, POMS)
timeFrame: Date of inclusion (baseline), after 6 and 12 weeks, after 6 months
measure: Stress questionnaire (Cohen Perceived Stress Scale, CPSS)
timeFrame: Date of inclusion (baseline), after 6 and 12 weeks, after 6 months
measure: Quality of Life questionnaire (WHO-5)
timeFrame: Date of inclusion (baseline), after 6 and 12 weeks, after 6 months
Other outcomes:
measure: Final questionnaire to record tolerability of fasting and nutrition, adverse effects
timeFrame: after 12 weeks
Locations:
city: Berlin
country: Germany
facility: Charité Hochschulambulanz für Naturheilkunde, Immanuel Krankenhaus Berlin
city: Berlin
country: Germany
facility: Charité University, Berlin, Department of Rheumatology and Clinical Immunology
Study officials:
affiliation: Charité Hochschulambulanz für Naturheilkunde, Immanuel Krankenhaus Berlin
name: Andreas Michalsen, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hartmann AM, Dell'Oro M, Kessler CS, Schumann D, Steckhan N, Jeitler M, Fischer JM, Spoo M, Kriegel MA, Schneider JG, Haupl T, Kandil FI, Michalsen A, Koppold-Liebscher DA. Efficacy of therapeutic fasting and plant-based diet in patients with rheumatoid arthritis (NutriFast): study protocol for a randomised controlled clinical trial. BMJ Open. 2021 Aug 11;11(8):e047758. doi: 10.1136/bmjopen-2020-047758.