An interventional study of Gluten-free, casein-free, low-glycemic-index diet in Thyroid Autoimmune Disease, Hashimoto's Thyroiditis and Graves Disease, sponsored by University of Barcelona. Not yet recruiting at 1 site in Andorra. Open to female participants aged 18 Years to 55 Years. Per ClinicalTrials.gov, last updated 2026-10-19.
Sponsored by University of Barcelona · Not applicable, Interventional, and Treatment
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:
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:
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:
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 ×100 In the intervention group, satisfactory adherence will be defined as a compliance rate of at least 90%.
Sample Size Calculation:
The sample size was calculated to detect a between-group difference of 30 IU/mL in the change of anti-TPO antibody concentrations, assuming a standard deviation of 45 IU/mL, a two-sided alpha level of 0.05, and 80% statistical power. Under these assumptions, 24 participants per group are required. To account for an anticipated attrition rate of approximately 20%, the target sample size has been increased to 30 participants per group (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.
90 studies on the registry are indexed under Hashimoto Disease; 26 are open to participants now.
This study's planned enrollment of 60 is close to the median of 60 across 43 interventional studies indexed under Hashimoto Disease.
Browse Hashimoto Disease studies →University of Barcelona is the lead sponsor of 97 studies on the registry; 28 are open to participants now.
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Exclusion Criteria:
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.
Other: Gluten-free, casein-free, low-glycemic-index 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.
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.
Change in serum anti-thyroid peroxidase (anti-TPO) antibody levels
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.
Time frame: Baseline (month 0) and month 12
Change in serum anti-thyroglobulin (anti-Tg) antibody levels
Serum anti-Tg antibodies (IU/mL) measured by immunoassay.
Time frame: Baseline, month 4, month 8 and month 12
Change in high-sensitivity C-reactive protein (hs-CRP)
Serum hs-CRP (mg/L) measured by immunoturbidimetry or nephelometry.
Time frame: Baseline, month 4, month 8 and month 12
Change in erythrocyte sedimentation rate (ESR)
ESR (mm/h) measured by the Westergren method.
Time frame: Baseline, month 4, month 8 and month 12
Change in fecal zonulin
Fecal zonulin measured by ELISA in a stool sample, as a marker of intestinal permeability.
Time frame: Baseline, month 4, month 8 and month 12
Change in thyroid function (TSH, free T4 and free T3)
Serum TSH, free T4 and free T3 measured by immunoassay.
Time frame: Baseline, month 4, month 8 and month 12
Change in micronutrient status (25-hydroxyvitamin D, ferritin and selenium)
Serum 25-hydroxyvitamin D, ferritin and selenium.
Time frame: Baseline, month 4, month 8 and month 12
Change in fatigue (Fatigue Severity Scale)
FSS: 9 items scored 1 to 7; total score is the mean of items (range 1-7). Higher scores indicate more fatigue.
Time frame: Monthly from baseline to month 12
Change in anxiety and depression (Hospital Anxiety and Depression Scale)
HADS: 14 items; anxiety and depression subscales each range 0-21. Higher scores indicate worse symptoms.
Time frame: Monthly from baseline to month 12
Change in health-related quality of life (WHOQOL-BREF)
WHOQOL-BREF: 26 items across physical, psychological, social and environmental domains. Higher scores indicate better quality of life.
Time frame: Monthly from baseline to month 12
Change in gastrointestinal symptoms (Gastrointestinal Symptom Rating Scale)
GSRS: 15 items scored 1 to 7 across 5 symptom dimensions. Higher scores indicate worse symptoms.
Time frame: Monthly from baseline to month 12
Change in weight
Weight (kg) measured with standard anthropometric techniques.
Time frame: Monthly from baseline to month 12
Change in body mass index
Weight and height, measured with standard anthropometric techniques, will be combined to report Body Mass Index in kg/m\^2 .
Time frame: Monthly from baseline to month 12
Change in waist circumference
Waist circunference (cm) measured with standard anthropometric techniques.
Time frame: Monthly from baseline to month 12
Dietary adherence (Nutritional Adherence Index)
Percentage of days with full compliance with the assigned diet, calculated from monthly dietary records.
Time frame: Monthly from baseline to month 12
Plan to share: No — 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).
Start is estimated for Jan 2027; primary completion for Dec 2027, 11 months later.
Of 19 interventional studies with no phase under Hashimoto Disease, half reached primary completion within 13 months of starting (the median), counting those still running; a quarter within 10 and three quarters within 65. This study's planned 11 months is below that.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is not yet recruiting, as verified in Oct 2026. You cannot join it, but the record below documents what was studied.
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