Exploratory Clinical Study on Fasting in Psoriasis and Psoriatic Arthritis (RiseFast)

Sociodemographic Measurements

age, education level, household income, employment status, marital status, complete family history of Psoriasis and/or Psoriatic Arthritis in first- and second-degree relatives, current and previous illness and co-morbidities, and current medications.

Time frame: Date of inclusion (baseline)

Medication intake

Systematized documentation of medication, main and secondary diagnoses using CRF.

Time frame: Date of inclusion (baseline), after 6 and 12 weeks

Quantification of Behavioral Factors

Sleeping habits, Physical Activity, Stress and Media Consumption via Likert Scales, range from 0 to 10 while higher values meaning a higher grade of agreement.

Time frame: Date of inclusion (baseline), after 6 and 12 weeks

Behavioral Factors: alcohol consumption

Number of alcoholic beverages on average per week in the last month.

Time frame: Date of inclusion (baseline), after 6 and 12 weeks

Behavioral Factors: smoking

Smoking status in packyears.

Time frame: Date of inclusion (baseline), after 6 and 12 weeks

Expectation questions

For fasting on a 10-point likert scale from 1 (nothing at all) to 10 (very strong).

Time frame: Date of inclusion (baseline)

Resting blood pressure (mmHg)

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

Pulse rate (bmp)

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

Abdominal circumference (cm)

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

Waist to Hip Ratio (cm)

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

Weight (kg)

Change in weight (kg)

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

Body Mass Index (kg/m2)

Change in Body Mass Index measured as weight (kg) and height (m) (kg/m\^2)

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

Bio-electrical impedance analysis (BIA)

Estimation of the body composition via bio-electrical impedance analysis (body fat and visceral fat in %)

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

Body Surface Area (BSA)

Body Surface Area (BSA) quantifies the percentage of skin affected by psoriasis, with one palm equating to approximately 1% of the total body surface. Values range from 0% to 100%, with higher percentages indicating greater skin involvement.

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

Nail Psoriasis Severity Index (NAPSI)

Nail Psoriasis Severity Index (NAPSI) evaluates the severity of nail psoriasis. It assesses each fingernail for specific features in the nail matrix (pitting, leukonychia, crumbling, red spots in the lunula) and nail bed (onycholysis, splinter hemorrhages, subungual hyperkeratosis, oil drop discoloration). Each nail is scored from 0 to 8, with higher scores indicating more severe nail involvement.

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

Criteria of minimal disease activity (MDA) or very low disease activity (VLDA)

Minimal Disease Activity (MDA) is a composite assessment of disease activity state in PsA. It includes 7 components: tender joint count (68) ≤ 1, swollen joint count (66) ≤ 1, Psoriasis Area Severity Index ≤ 1/Body Surface Area ≤ 3, enthesitis≤ 1, patient global assessment of disease activity VAS ≤ 20, pain VAS ≤ 15 and HAQ-DI ≤ 0.5. MDA requires 5 out of 7 components to be met Very Low Disease Activity (VLDA) is a stricter composite assessment of disease activity state in Psoriatic Arthritis (PsA). It includes 7 components, all of which must be fulfilled to achieve VLDA: tender joint count (68): ≤ 1; Swollen joint count (66): ≤ 1; Psoriasis Area and Severity Index (PASI): ≤ 1 or Body Surface Area (BSA): ≤ 1%; Enthesitis count: 0 (no active enthesitis); Patient global assessment of disease activity (VAS): ≤ 20; Pain assessment (VAS): ≤ 15; Health Assessment Questionnaire Disability Index (HAQ-DI): ≤ 0.5

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

68 Tender Joint Count

Change in Tender Joint Count at Week 12 as compared to baseline, with a maximum possible range between 0 to 68 with higher values indicating a worsening of the symptoms.

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

66 Swollen Joint Count

Change in Swollen Joint Count at Week 12 as compared to baseline, with a maximum possible range between 0 to 66 with higher values indicating a worsening of the symptoms.

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

Leeds Enthesitis Index (LEI)

Leeds Enthesitis Index (LEI) is used to assess enthesitis in psoriatic arthritis (PsA). It evaluates tenderness (1 = present, 0 = absent) at six specific sites: the lateral epicondyles (elbows), medial femoral condyles (knees), and Achilles tendon insertions (heels) on both sides of the body. The total score ranges from 0 (no tenderness) to 6 (tenderness at all sites).

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

ACR20/50 criteria

ACR20/50 and ACR50 response criteria assess treatment efficacy in psoriatic arthritis. Achievement of ACR20 requires a ≥20% improvement in both the tender joint count (68 joints) and the swollen joint count (66 joints), in addition to a ≥20% improvement in at least three of the following five domains: patient global assessment of disease activity (VAS 0-100), physician global assessment of disease activity (VAS 0-100), pain assessment (VAS 0-100), physical function (e.g., HAQ-DI), and acute-phase reactants (CRP or ESR). Similarly, ACR50 requires a ≥50% improvement in these parameters, reflecting a more substantial reduction in disease activity.

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

Health Assessment Questionnaire Disability Index (HAQ-DI)

Change from Baseline in the HAQ after 12 weeks, range from 0 to 3 while higher values meaning a higher grade of disability.

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

Quality of Life questionnaire (WHO-5)

Change from Baseline in the WHO-5, range from 0 to 100 %, higher values meaning a higher grade of well-being.

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

Dermatology Life Quality Index (DLQI)

Changes from Baseline in the DLQI after 12 weeks, range from 0 to 3, higher values meaning a lower grade of life quality.

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

EULAR Psoriatic Arthritis Impact of Disease (PsAID12)

Changes from Baseline in the PsAID-12, formed of 12 questions, each evaluated on a 0-10 numeric rating scale, where a higher score reflects a greater impact of PsA.

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

Subjective strength of the main complaint (Visual Analogue Scale)

The Visual Analog Scale for Pain (VAS Pain) and the Visual Analog Scale for Skin Complaints (VAS Skin Complaints) both range from 0 to 10, with higher values indicating more severe symptoms.

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

Short Form 36

36-Item Short Form Survey (SF-36) used as Quality of life assessment, containing 36 items, the total score range from 0 to 100, a high score represents a high quality of life).

Time frame: Date of inclusion (baseline) and after 12 weeks

Food selection

Nutritional history via dietary record (3-day food record)

Time frame: Date of inclusion (baseline), after 4 and 9 weeks

Dietary Behaviour

The Food Frequency Questionnaire (FFQ) records dietary behaviors such as mealtimes, frequency of food intake, food preferences, and fasting experiences.

Time frame: Date of inclusion (baseline), after 6 and 12 weeks

Differential blood count

Analysis of different types of blood cells to assess immune status and detect possible infections or inflammations.

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

CRP in milligram per liter (mg/L)

CRP (C-reactive protein) as a marker of inflammatory conditions is used to assess acute inflammation and monitor the effects of prolonged fasting and plant-based nutrition. Higher scores indicate more inflammation.

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

Creatinine in µmol per liter (µmol/L)

Biomarker of renal function and muscle metabolism.

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

Ketone bodies (mmol/l)

Indicators of fat metabolism and ketosis, analyzed for metabolic adaptations.

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

Glucose (mg/dl)

Fasting blood sugar measurement to monitor metabolic changes.

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

Hepatic transaminases (ALAT, ASAT) and Gamma glutamyl transpeptidase (y-GT)

* ALAT in units per liter (U/L) * ASAT (U/L) * gamma-GT (U/l)

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

Electrolytes

* calcium in millimol per liter (mmol/L) * potassium (mmol/L) * sodium (mmol/L)

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

Flow cytometry: Phenotyping of immune cells

Determination of cytometric parameters to assess changes in cell activation and quantify alterations in the absolute and/or relative sizes of immune cell subpopulations (e.g., classical, intermediate, and non-classical monocytes; naïve and memory T-cells; B-cell differentiation to plasmablasts and plasma cells). In addition, gene expression analysis of immune cells using Affymetrix whole genome microarrays and RNA sequencing (RNAseq) will be conducted to explore transcriptional patterns and identify markers that could reveal relevant immune cell subpopulations, which are not yet captured in the cytometric phenotyping screen.

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

Cytokine profile

Quantification of pro- and anti-inflammatory cytokines (e.g., IL-6, IL-17, TNF-α, IL-10) using multiplex ELISA or Luminex technology.

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

Functional immune cell tests

Ex vivo stimulation of immune cells to measure proliferation capacity and cytokine secretion.

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

NK cell activity

Determination of cytotoxic function of natural killer (NK) cells.

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

Autoantibodies

Screening for disease-relevant autoantibodies associated with immune dysregulation.

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

Gene expression analysis

RNA sequencing of whole blood samples to assess diet-induced transcriptomic changes.

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

Epigenetic analysis

DNA methylation profiling to examine nutrition-related epigenetic modifications.

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

Metabolomics

Targeted and untargeted metabolite profiling of energy, lipid, and amino acid metabolism. * triglycerides (mg/dl) * total cholesterol (mg/dl) * LDL cholesterol (mg/dl) * non-HDL cholesterol (mg/dl) * HDL cholesterol (mg/dl)

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

Creatine kinase (U/L)

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

Uric acid (µmol/L)

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

Biobanking (for future proteomics analysis)

Sample storage for additional protein analysis if funding is secured.

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

Gut microbiota characterization

Molecular profiling of the highly individualized intestinal microbiota composition is performed through 16S rDNA gene sequencing of stool samples, aiming to identify fasting- and diet-induced alterations in the gut microbiota.

Time frame: Date of inclusion (baseline), day 8 or first stool after fasting, after 6 and 12 weeks

Lactate dehydrogenase (LDH) (U/L)

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

Serum Vitamin B12 Levels (ng/l)

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

Estimated glomerular filtration rate (eGFR) in milliliter per minute (mL/min)

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

Total protein in grams per liter (g/L)

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

Serum 25-hydroxyvitamin D (25(OH)D) levels in nmol/l and Serum 1,25-Dihydroxyvitamin D [1,25(OH)2D3] levels in nmol/l

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks

Albumin in grams per liter (g/L)

Time frame: Date of inclusion (baseline), day 8, after 6 and 12 weeks