The Effect of Fermented Grape Juice Consumption on Fibromyalgia Patients

February 7, 2026 updated by: Tuba Kahraman, Hacettepe University

Determination of the Effect of Fermented Grape Juice Consumption on Oxidative Stress and Inflammation Biomarkers and SIRT-1 Levels in Fibromyalgia Patients

The goal of this clinical trial is to learn if a traditional grape-based fermented drink called hardaliye helps treat fibromyalgia in adult women. We will also learn whether adding hardaliye to a personalized nutrition plan works better than using either one alone.

The main questions are:

Does diet + hardaliye improve antioxidant status and lower oxidative stress more than diet only or hardaliye only? Does diet + hardaliye lower inflammation (TNF-α, IL-6, hs-CRP) and raise SIRT1 levels? Do these changes relate to less pain and better symptoms (fibromyalgia impact, gut symptoms, sleep, mood)? Are there benefits for weight, waist size, blood pressure, and blood lipids?

How the groups are compared:

Researchers will compare three groups for 8 weeks:

Diet + Hardaliye (personalized medical nutrition plan + one 200 mL bottle of hardaliye daily) Diet only (personalized medical nutrition plan) Hardaliye only (usual diet + one 200 mL bottle of hardaliye daily)

Participants will:

Drink one 200 mL bottle of hardaliye each day if assigned to Diet + Hardaliye or Hardaliye only Follow a personalized nutrition plan if assigned to Diet + Hardaliye or Diet only Visit the clinic at the start and end of the study, with brief check-ins around weeks 2, 4, and 6 Give blood samples before and after the 8-week period Complete short questionnaires on pain, fibromyalgia impact, gut symptoms, sleep, and mood Keep simple logs of daily drink intake and diet plan adherence, and report any side effects

Who can join:

Adult women (20-40 years) with doctor-diagnosed fibromyalgia and BMI 25.0-29.9 kg/m² who meet the study's health and medication criteria.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a single-center, parallel-group, randomized clinical trial with three intervention conditions implemented over an 8-week period. After screening and baseline procedures, participants are assigned in a 1:1:1 ratio using a computer-generated block randomization sequence prepared by an independent researcher not otherwise involved in study conduct. Allocation concealment is maintained using sequentially numbered, opaque, sealed envelopes opened only after confirming eligibility.

Due to the dietary nature of the interventions, participant-level blinding is not feasible. However, biospecimen handling and laboratory analyses are performed on coded (anonymized) samples; laboratory personnel remain blinded to group assignment and time point to minimize measurement bias.

Personalized medical nutrition therapy (MNT) is delivered using a standardized counseling framework with individualized targets. Resting metabolic rate is estimated using the Mifflin-St Jeor equation, and daily energy prescription is derived using physical activity level (PAL). Macro-distribution targets are standardized (10-20% protein, 45-60% carbohydrate, 25-30% fat), with saturated fat <7% of energy and trans fat <1% to align with guidance-based cardiometabolic risk control.

To reduce confounding from background polyphenol exposure, participants are instructed to avoid high-polyphenol red/purple fruits and vegetables according to protocol-defined lists; diet plans are structured as three main meals plus 2-3 snacks, and standardized exchange lists are provided to support adherence.

Hardaliye intervention (product handling and quality assurance): The study beverage is sourced from a traditional producer in Kırklareli and manufactured via controlled spontaneous fermentation without starter culture.

Hardaliye is dispensed in 200 mL bottles and distributed weekly under cold-chain conditions; participants are instructed to consume the beverage daily within a consistent intake window (16:00-16:30) to standardize exposure timing.

To ensure batch-to-batch consistency, each production batch undergoes predefined acceptance checks (°Brix, pH, and titratable acidity), and key compositional markers are measured post-bottling (total phenolics via Folin-Ciocalteu, total monomeric anthocyanins via pH-differential method, and antioxidant capacity via ABTS-based TEAC). Analytical repeatability is monitored (replicates/parallel runs; CV target <10% with repeat testing if unmet).

Batches outside acceptance ranges (e.g., °Brix 20.5-21.8; pH 3.50-4.00; acidity 0.68-0.75 g/100 mL; and protocol-defined total phenolic/anthocyanin targets) are excluded from participant distribution.

Where relevant, chromatographic confirmation (HPLC-DAD) is used to verify the phenolic profile of the study product and support linkage of total phenolic estimates to compound-level composition.

Participants complete an initial screening visit followed by a baseline (Day 0) visit and an end-of-intervention (Week 8) visit, with brief interim check-ins at Weeks 2, 4, and 6 for adherence review and systematic safety monitoring. Interim contacts include beverage count/log review, reinforcement of dietary counseling where applicable, and adverse event solicitation/documentation.

Adherence is operationalized as ≥80% compliance with the assigned beverage intake and/or nutrition therapy targets; intake and adherence are captured using simple participant logs reviewed at each contact.

Dietary intake is assessed using structured food records collected at multiple time points (7-day records at baseline, Week 4, and Week 8; and additional 3-day records during specified weeks) to quantify energy and nutrient intake and to support adherence monitoring. Nutrient analyses are performed using BeBIS software and interpreted against national reference intakes.

Dietary polyphenol exposure is estimated using Phenol-Explorer (v3.6) to derive total polyphenols and relevant subclasses; an antioxidant diet quality score (DAQS) is calculated based on intake of key antioxidant nutrients. Physical activity is monitored via 24-hour recall on diary days, and PAL is derived using activity-specific PAR values combined with Mifflin-St Jeor BMR estimates to support stability of lifestyle exposure during follow-up.

Fasting venous blood is collected at baseline and Week 8 and processed according to institutional standard operating procedures (timing, centrifugation, aliquoting, storage). Samples are labeled with coded identifiers to preserve analytical blinding, and assays are performed following validated methods and kit instructions with internal QC steps documented prospectively.

Data are captured in structured case report forms and reconciled against visit checklists, distribution records, and participant logs. Primary analyses follow an intention-to-treat approach. Group differences in change over time are evaluated using repeated-measures modeling (e.g., linear mixed-effects models including group, time, and group×time interaction), with prespecified sensitivity analyses based on adherence and protocol deviations; missing-data handling and multiplicity procedures are defined in the statistical analysis plan.

Study Type

Interventional

Enrollment (Estimated)

45

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Turkey (Türkiye)
    • Istanbul
      • Istanbul, Istanbul, Turkey (Türkiye), 34098
        • İstanbul University-Cerrahpaşa Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Female, 20-40 years
  • BMI 25.0-29.9 kg/m²
  • FM per 2016 ACR criteria; abdominal pain/cramp per SSS sub-item
  • MEDAS ≤5 at screening.
  • Willing to maintain habitual activity and comply with assigned intervention; able to provide informed consent.

Exclusion Criteria:

  • Age <20 or >40
  • BMI ≤24.99 or ≥30.0 kg/m²
  • Professional athletes; night-shift workers
  • Food allergies; acute infection; antibiotic use within past month or during intervention.
  • Use (past 3 months) of dietary supplements; recent weight-loss or special diets (e.g., ketogenic).
  • Pregnancy/lactation; menopause.
  • Major hepatic/renal/cardiac/immune disease; chronic GI diseases; diabetes; CNS disorders; cancer; thyroid disease; severe pulmonary disease. Inflammatory arthritis/autoimmune disease impacting weight; medications including corticosteroids, estrogens, analgesics/anti-inflammatories, anti-diabetic or lipid-lowering drugs.
  • Severe psychiatric illness/substance use; heavy alcohol/smoking.
  • High recent intake of grape juice/molasses; excess tea/coffee (≥7 cups/day).
  • Adherence <80% to beverage or MNT during run-in/screening.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Medical Nutrition Therapy + Hardaliye

Assigned Interventions:

Medical Nutrition Therapy (MNT) Hardaliye (200 mL/day)

Arm Description: Participants receive individualized MNT and consume 200 mL hardaliye once daily during the intervention period.
Behavioral: Medical Nutrition Therapy (MNT)
Individually tailored medical nutrition therapy delivered using a standardized counseling framework, energy prescription derived from predictive equations and physical activity level, with standardized macronutrient targets and follow-up reinforcement per protocol.
Other: Hardaliye (200 mL/day)
Traditional grape-based fermented beverage dispensed in 200 mL bottles; participants consume 200 mL once daily for the intervention period with standardized intake instructions and product handling.
Experimental: Medical Nutrition Therapy

Assigned Interventions:

Medical Nutrition Therapy (MNT) Arm Description: Participants receive individualized MNT; no study beverage is provided.
Behavioral: Medical Nutrition Therapy (MNT)
Individually tailored medical nutrition therapy delivered using a standardized counseling framework, energy prescription derived from predictive equations and physical activity level, with standardized macronutrient targets and follow-up reinforcement per protocol.
Experimental: Hardaliye

Assigned Interventions:

Hardaliye (200 mL/day) Arm Description: Participants consume 200 mL hardaliye once daily and continue usual diet; no MNT is provided.
Other: Hardaliye (200 mL/day)
Traditional grape-based fermented beverage dispensed in 200 mL bottles; participants consume 200 mL once daily for the intervention period with standardized intake instructions and product handling.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Fibromyalgia Impact Questionnaire Revised
Time Frame: Baseline to Week 8
Change in FIQR (0-100); lower scores indicate less symptom burden and better function.
Baseline to Week 8
Pain Severity (Visual Analog Scale, VAS)
Time Frame: Baseline to Week 8
Change in 0-10 cm VAS for average pain; lower scores reflect less pain.
Baseline to Week 8
Gastrointestinal symptoms (Gastrointestinal Symptom Rating Scale, GSRS)
Time Frame: Baseline to Week 8

Change in Gastrointestinal Symptom Rating Scale (GSRS) total score and subscale scores (abdominal pain, reflux, diarrhea, dyspepsia/indigestion, constipation).

The GSRS includes 15 items, each rated for the past week on a 7-point scale (1 = no discomfort, 7 = very severe discomfort). Higher scores indicate worse gastrointestinal symptoms and lower scores indicate fewer/milder symptoms.

Total score (sum of 15 items): 15-105 Abdominal pain subscale (Items 1, 4, 5; sum): 3-21 Reflux subscale (Items 2, 3; sum): 2-14 Dyspepsia/Indigestion subscale (Items 6, 7, 8, 9; sum): 4-28 Diarrhea subscale (Items 11, 12, 14; sum): 3-21 Constipation subscale (Items 10, 13, 15; sum): 3-21
Baseline to Week 8
Sleep Quality (Pittsburgh Sleep Quality Index, PSQI)
Time Frame: Baseline to Week 8
Change in PSQI global score (0-21); lower scores indicate better sleep quality.
Baseline to Week 8
Depressive Symptoms (Beck Depression Inventory, BDI)
Time Frame: Baseline to Week 8
Change in BDI total score (0-63); lower scores indicate fewer depressive symptoms.
Baseline to Week 8

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total Antioxidant Status (TAS; μmol Trolox eq/L)
Time Frame: Baseline to Week 8
Change in circulating antioxidant capacity; higher values suggest stronger systemic antioxidant defense.
Baseline to Week 8
Total Oxidant Status (TOS; μmol H₂O₂ eq/L)
Time Frame: Baseline to Week 8
Change in cumulative oxidant load; lower values indicate reduced oxidative pressure.
Baseline to Week 8
Oxidative Stress Index (OSI = TOS×100 / TAS)
Time Frame: Baseline to Week 8
Ratio index of oxidant burden to antioxidant capacity; lower values denote better redox balance.
Baseline to Week 8
Plasma Malondialdehyde (MDA; TBARS method)
Time Frame: Baseline to Week 8
Change in lipid peroxidation marker; lower levels indicate less oxidative membrane damage.
Baseline to Week 8
Serum 8-Hydroxy-2'-deoxyguanosine (8-OHdG)
Time Frame: Baseline to Week 8
Change in DNA oxidative damage marker; lower concentrations suggest reduced nucleic acid oxidation.
Baseline to Week 8
Inflammatory biomarkers (TNF-α, IL-6, hs-CRP)
Time Frame: Baseline to Week 8
Changes in systemic inflammation; reductions indicate attenuation of low-grade inflammatory activity.
Baseline to Week 8
Serum Sirtuin-1(SIRT1)
Time Frame: Baseline to Week 8
Change in SIRT1 concentration (ELISA); higher levels are consistent with enhanced cellular stress-response signaling.
Baseline to Week 8

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Body Weight
Time Frame: Baseline to Week 8
Body weight measured in light clothing without shoes using a calibrated scale. Units: kilograms (kg). Higher values indicate greater body mass.
Baseline to Week 8
Height
Time Frame: Baseline to Week 8
Standing height measured without shoes using a calibrated stadiometer. Units: centimeters (cm). Height is collected primarily to compute BMI (kg/m²). Higher values indicate greater stature.
Baseline to Week 8
Body Mass Index (BMI)
Time Frame: Baseline to Week 8
BMI calculated as weight (kg) / height (m²) using measured weight and height. Units: kg/m². Higher values indicate higher adiposity-related risk.
Baseline to Week 8
Waist Circumference
Time Frame: Baseline to Week 8
Waist circumference measured at a standardized anatomical site using a non-elastic tape. Units: centimeters (cm). Higher values indicate greater central adiposity.
Baseline to Week 8
Waist-to-Hip Ratio (WHR)
Time Frame: Baseline to Week 8
WHR calculated as waist circumference (cm) / hip circumference (cm) from standardized tape measurements. Units: ratio (unitless). Higher values indicate greater central fat distribution.
Baseline to Week 8
Systolic Blood Pressure (SBP)
Time Frame: Baseline to Week 8
Seated systolic blood pressure measured after rest using a validated device per standardized procedure. Units: mmHg. Higher values indicate higher systolic pressure.
Baseline to Week 8
Diastolic Blood Pressure (DBP)
Time Frame: Baseline to Week 8
Seated diastolic blood pressure measured after rest using a validated device per standardized procedure. Units: mmHg. Higher values indicate higher diastolic pressure.
Baseline to Week 8
Lipid Profile (total cholesterol, HDL-C, LDL-C, triglycerides)
Time Frame: Baseline to Week 8
Changes indicate potential effects on atherogenic risk.
Baseline to Week 8
Dietary Polyphenol Intake (Phenol-Explorer-based total and subclasses)
Time Frame: Baseline to Week 8
Estimated change in total/flavonoids/phenolic acids/flavanols/lignans; higher intake supports exposure to bioactive compounds.
Baseline to Week 8
Dietary Antioxidant Quality Score (DAQS)
Time Frame: Baseline to Week 8
Description: Change in Dietary Antioxidant Quality Score (DAQS), a unitless composite score ranging from 0 to 5 derived from dietary intakes of vitamins A, C, and E, and the minerals zinc and selenium. For each nutrient, participants receive 1 point if their intake is ≥ 2/3 of the age- and sex-specific Recommended Dietary Allowance (RDA) / Dietary Reference Intake (DRI), and 0 points otherwise. Points are summed across the 5 nutrients (minimum 0, maximum 5). Higher DAQS indicates better dietary antioxidant quality (more adequate antioxidant-related nutrient intake), whereas lower scores indicate poorer dietary antioxidant quality.
Baseline to Week 8

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hacettepe University

Investigators

  • Study Director: Aylin Ayaz, Prof.Dr., Hacettepe University Nutrition and Dietetics Department

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

February 15, 2026

Primary Completion (Estimated)

December 15, 2026

Study Completion (Estimated)

February 15, 2027

Study Registration Dates

First Submitted

December 3, 2025

First Submitted That Met QC Criteria

February 7, 2026

First Posted (Actual)

February 11, 2026

Study Record Updates

Last Update Posted (Actual)

February 11, 2026

Last Update Submitted That Met QC Criteria

February 7, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1422809

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

I haven't started working on it yet and made progress.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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