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Impact of Restrictive Diets on Inflammation and Quality of Life in Autoimmune Thyroiditis (TAILOR)

1 november 2026 bijgewerkt door: Natalia Toro Funes, University of Barcelona

Impact of Restrictive Diets Targeting Inflammatory Dietary Components (Gluten, Casein, and High-glycemic-index Carbohydrates) on Inflammatory Markers and Quality of Life in Patients With Autoimmune Thyroiditis

The purpose of this clinical trial is to evaluate whether a dietary intervention can improve clinical and immunological outcomes in women with autoimmune thyroid disease (AITD), including Hashimoto's thyroiditis and Graves' disease. The study will enroll premenopausal women aged 18 to 55 years.

The dietary intervention consists of the simultaneous exclusion of three groups of potentially pro-inflammatory dietary components:

  • Gluten-containing cereals, including wheat, barley, and rye.
  • Casein, the main protein found in milk and dairy products.
  • High-glycemic-index carbohydrates, such as refined sugar, white bread, and white rice.

The primary objective is to determine whether the dietary intervention reduces serum levels of anti-thyroid peroxidase (anti-TPO) antibodies, which are markers of thyroid autoimmunity.

Secondary objectives include evaluating whether the intervention improves:

  • Fatigue and energy levels.
  • Mood and emotional well-being.
  • Gastrointestinal symptoms.
  • Health-related quality of life.

Women following the dietary intervention will be compared with women who continue their habitual diet to assess the effectiveness of the intervention. Group allocation will be based on participants' choice at study enrollment.

Participants will:

  • Follow either the dietary intervention or their usual diet for 12 months while continuing their prescribed medical treatment.
  • Attend four study visits: at baseline and after 4, 8, and 12 months.
  • Undergo anthropometric assessments (body weight and waist circumference), blood sampling, stool collection, and a telemedicine consultation with a thyroid specialist at each visit.
  • Complete brief online questionnaires every month to assess dietary adherence, fatigue, mood, gastrointestinal symptoms, and quality of life.

Studie Overzicht

Toestand

Nog niet aan het werven

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

Background:

Previous studies have investigated the effects of gluten-free diets, casein-free diets, or the restriction of high-glycemic-index carbohydrates separately in individuals with autoimmune thyroid disease (AITD), yielding heterogeneous and inconclusive findings. The present study aims to evaluate the combined effect of simultaneously excluding these dietary components on immunological, clinical, and patient-reported outcomes in women with AITD. The dietary intervention is intended as a nutritional strategy under investigation and is not designed to replace standard medical treatment or routine clinical care.

Dietary Intervention:

Participants assigned to the intervention group will simultaneously eliminate gluten-containing cereals (wheat, barley, and rye), dairy-derived casein, and high-glycemic-index carbohydrates from the start of the study. No sequential elimination or reintroduction phases are planned. The study periods (months 0-4, 4-8, and 8-12) correspond exclusively to predefined assessment intervals. Apart from the dietary exclusions under investigation, participants will be advised to maintain a stable dietary pattern with comparable energy intake and macronutrient distribution throughout the study.

Group Allocation:

This is a prospective, non-randomized study. Group assignment will be determined at baseline, prior to initiation of the intervention, according to each participant's willingness and ability to follow the dietary protocol. To minimize potential selection bias associated with the absence of randomization, propensity score methods based on baseline characteristics, including age, body mass index (BMI), baseline anti-thyroid peroxidase antibody (anti-TPO) levels, thyroid-related treatment, and relevant lifestyle factors, will be incorporated into the statistical analysis through adjustment, stratification, or inverse probability of treatment weighting, as appropriate.

Adherence Assessment:

Adherence to the dietary protocol will be evaluated using a Nutritional Adherence Index calculated as: Adherence (%) = (days with complete compliance / total days evaluated) x 100. In the intervention group, satisfactory adherence will be defined as a compliance rate of at least 90%.

Sample Size Calculation:

The sample size is based on the primary outcome (change in anti-TPO antibody concentrations from baseline to month 12). In a comparable non-randomised trial of a gluten-free diet in women with Hashimoto's thyroiditis (Krysiak R, Szkróbka W, Okopień B. Exp Clin Endocrinol Diabetes. 2019;127(7):417-422. doi: 10.1055/a-0653-7108), the standard deviations of the 6-month change in anti-TPO were 105 and 25 U/mL (pooled SD approximately 74 U/mL), with a between-group difference of 229 U/mL. Assuming a pooled SD of 74 IU/mL, a two-sided alpha of 0.05 and 80% power, 24 evaluable participants per group allow detection of a between-group difference of about 60 IU/mL, approximately one quarter of the effect previously reported. Allowing for approximately 20% attrition, 30 participants per group will be recruited (total N = 60).

Statistical Analysis:

The primary analysis will evaluate changes in anti-TPO antibody concentrations between groups using multivariable regression models adjusted for potential confounding factors. Longitudinal changes across follow-up visits will be assessed using repeated-measures analysis of variance (ANOVA) or linear mixed-effects models, as appropriate. Both intention-to-treat and per-protocol analyses will be performed. Missing data will be addressed using multiple imputation methods.

Safety Monitoring:

Participants will be monitored throughout the study for potential adverse effects related to the dietary intervention. Predefined safety criteria include unintentional weight loss exceeding 5% of body weight within one month, clinically significant thyroid dysfunction requiring treatment adjustment, persistent gastrointestinal symptoms, evidence of nutritional deficiency, and significant psychological distress. Adverse events will be evaluated within 48 hours of notification, and serious adverse events will be reported to the relevant Ethics Committee within 7 calendar days, in accordance with applicable regulations.

Studietype

Ingrijpend

Inschrijving (Geschat)

60

Fase

  • Niet toepasbaar

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studiecontact

Studie Locaties

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar tot 55 jaar (Volwassen)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Vrouw

Beschrijving

Inclusion Criteria:

  • Women aged 18 to 55 years, of reproductive age and not menopausal
  • Confirmed diagnosis of autoimmune thyroiditis (Hashimoto's thyroiditis or Graves' disease) based on clinical, hormonal and immunological criteria
  • Under clinical follow-up by an endocrinology unit
  • Stable thyroid function; if on pharmacological treatment, stable for at least 3 months before study entry
  • No relevant nutritional deficiencies (vitamin D, selenium, zinc, iron or vitamin B12), or adequately supplemented according to clinical criteria
  • Willingness to participate in a supervised nutritional program and signed informed consent

Exclusion Criteria:

  • Other active autoimmune or systemic diseases (e.g., lupus, multiple sclerosis, type 1 diabetes), active inflammatory bowel disease, peptic ulcer or intestinal infections
  • Established menopause or perimenopause
  • Body mass index outside the range 18.5-29.9 kg/m2
  • Pregnancy or breastfeeding
  • Use of immunosuppressive drugs or corticosteroids
  • Previous restrictive diets
  • Severe food intolerances or conditions preventing adherence to the protocol (e.g., wheat allergy, celiac disease, casein allergy)

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Niet-gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Triple-restriction diet

Participants will follow a dietary protocol involving the simultaneous exclusion of gluten-containing cereals, dairy-derived casein, and high-glycemic-index carbohydrates from baseline through month 12. The intervention will be supported by individualized dietary guidance and monthly monitoring of adherence to the protocol.

Participants in the intervention group will follow a dietary protocol consisting of the simultaneous exclusion of gluten-containing cereals (including wheat, barley, rye, spelt, and foods containing gluten), dairy products containing casein (including milk, yogurt, cheese, cream, butter, and related products), and high-glycemic-index carbohydrates (including refined sugar, refined grain products, white rice, and pastries). The dietary intervention will be maintained continuously for 12 months. No investigational medications, mandatory dietary supplements, or other therapeutic interventions will be administered as part of the study protocol.

Geen tussenkomst: Usual diet

Participants in the control group will continue their habitual diet without prescribed dietary modifications or restrictions. Dietary intake will be monitored using food frequency questionnaires and monthly dietary records. Participants will undergo the same follow-up schedule, clinical assessments, biological sample collection, and patient-reported outcome evaluations as the intervention group over the 12-month study period.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Change in serum anti-thyroid peroxidase (anti-TPO) antibody levels
Tijdsspanne: Baseline (month 0) and month 12

Serum anti-TPO antibodies (IU/mL) measured by immunoassay in a fasting morning blood sample. Change from baseline to month 12 is compared between groups.

Baseline (month 0) and month 12

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Change in serum anti-thyroglobulin (anti-Tg) antibody levels
Tijdsspanne: Baseline, month 4, month 8 and month 12

Serum anti-Tg antibodies (IU/mL) measured by immunoassay.

Baseline, month 4, month 8 and month 12
Change in high-sensitivity C-reactive protein (hs-CRP)
Tijdsspanne: Baseline, month 4, month 8 and month 12

Serum hs-CRP (mg/L) measured by immunoturbidimetry or nephelometry.

Baseline, month 4, month 8 and month 12
Change in erythrocyte sedimentation rate (ESR)
Tijdsspanne: Baseline, month 4, month 8 and month 12

ESR (mm/h) measured by the Westergren method.

Baseline, month 4, month 8 and month 12
Change in fecal zonulin
Tijdsspanne: Baseline, month 4, month 8 and month 12

Fecal zonulin measured by ELISA in a stool sample, as a marker of intestinal permeability.

Baseline, month 4, month 8 and month 12
Change in thyroid function (TSH, free T4 and free T3)
Tijdsspanne: Baseline, month 4, month 8 and month 12

Serum TSH, free T4 and free T3 measured by immunoassay.

Baseline, month 4, month 8 and month 12
Change in micronutrient status (25-hydroxyvitamin D, ferritin and selenium)
Tijdsspanne: Baseline, month 4, month 8 and month 12

Serum 25-hydroxyvitamin D, ferritin and selenium.

Baseline, month 4, month 8 and month 12
Change in fatigue (Fatigue Severity Scale)
Tijdsspanne: Monthly from baseline to month 12

FSS: 9 items scored 1 to 7; total score is the mean of items (range 1-7). Higher scores indicate more fatigue.

Monthly from baseline to month 12
Change in anxiety and depression (Hospital Anxiety and Depression Scale)
Tijdsspanne: Monthly from baseline to month 12

HADS: 14 items; anxiety and depression subscales each range 0-21. Higher scores indicate worse symptoms.

Monthly from baseline to month 12
Change in health-related quality of life (WHOQOL-BREF)
Tijdsspanne: Monthly from baseline to month 12

WHOQOL-BREF: 26 items across physical, psychological, social and environmental domains. Higher scores indicate better quality of life.

Monthly from baseline to month 12
Change in gastrointestinal symptoms (Gastrointestinal Symptom Rating Scale)
Tijdsspanne: Monthly from baseline to month 12

GSRS: 15 items scored 1 to 7 across 5 symptom dimensions. Higher scores indicate worse symptoms.

Monthly from baseline to month 12
Change in weight
Tijdsspanne: Monthly from baseline to month 12

Weight (kg) measured with standard anthropometric techniques.

Monthly from baseline to month 12
Change in body mass index
Tijdsspanne: Monthly from baseline to month 12

Weight and height, measured with standard anthropometric techniques, will be combined to report Body Mass Index in kg/m^2 .

Monthly from baseline to month 12
Change in waist circumference
Tijdsspanne: Monthly from baseline to month 12

Waist circumference (cm) measured with standard anthropometric techniques.

Monthly from baseline to month 12
Dietary adherence (Nutritional Adherence Index)
Tijdsspanne: Monthly from baseline to month 12

Percentage of days with full compliance with the assigned diet, calculated from monthly dietary records.

Monthly from baseline to month 12

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Medewerkers

Onderzoekers

  • Hoofdonderzoeker: Laurence Lestang Doublet, MSc, RD, Universidad Internacional de Valencia
  • Hoofdonderzoeker: Natalia Toro Funes, PhD, Universidad de Barcelona
  • Studie directeur: Mariana Silva López, PhD, Universidad Internacional de Valencia

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Geschat)

1 januari 2027

Primaire voltooiing (Geschat)

31 december 2028

Studie voltooiing (Geschat)

31 december 2028

Studieregistratiedata

Eerst ingediend

6 oktober 2026

Eerst ingediend dat voldeed aan de QC-criteria

13 oktober 2026

Eerst geplaatst (Werkelijk)

19 oktober 2026

Updates van studierecords

Laatste update geplaatst (Werkelijk)

4 november 2026

Laatste update ingediend die voldeed aan QC-criteria

1 november 2026

Laatst geverifieerd

1 november 2026

Meer informatie

Termen gerelateerd aan deze studie

Andere studie-ID-nummers

  • CEIDTDM2026_01

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

NEE

Beschrijving IPD-plan

Individual participant data will not be shared. Data are pseudonymized during the study and irreversibly anonymized after publication; results will be reported in aggregate form only, in accordance with the informed consent and applicable data protection regulations (GDPR and Andorran Law 29/2021).

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .