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

Changes in disease activity measured by the Psoriasis Area and Severity Index (PASI) after 12 weeks compared to baseline.

Changes in disease activity measured by the Disease Activity index for Psoriatic Arthritis (DAPSA) after 12 weeks compared to baseline.

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.

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

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.

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

Smoking status in packyears.

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

Change in weight (kg)

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

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

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.

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.

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

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.

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.

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).

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.

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

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

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

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.

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.

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).

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

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

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

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.

Biomarker of renal function and muscle metabolism.

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

Fasting blood sugar measurement to monitor metabolic changes.

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

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

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.

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

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

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

Screening for disease-relevant autoantibodies associated with immune dysregulation.

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

DNA methylation profiling to examine nutrition-related epigenetic modifications.

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)

Sample storage for additional protein analysis if funding is secured.

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.

Measurement of tolerability of fasting and nutrition as well as adverse effects via Likert Scales, range from 0 to 10 while higher values meaning a higher grade of agreement.