Evaluation of the effect of L-theanine in patients with hyperthyroidism treated with methimazole: A two-group randomized placebo-controlled clinical trial

To evaluate the effects of L-theanine supplementation alongside methimazole on anxiety, sleep quality, fatigue, thyroid hormones, cortisol, and clinical and laboratory parameters in patients with

A randomized, placebo-controlled, parallel-group clinical trial involving 60 participants equally allocated to two groups using block randomization. Participants and outcome assessors will be blinded

Patients will be recruited consecutively from an endocrinology clinic in Dezful. Following eligibility assessment and methimazole stabilization, participants will receive a four-week intervention, with assessments at baseline and post-intervention

Patients aged 18–60 years with hyperthyroidism receiving methimazole for at least four weeks, with informed consent and no recent L-theanine or sedative use. Withdrawal criteria include serious adverse events, pregnancy, severe hepatic, renal or cardiac disease, adherence below 80%, and voluntary withdrawal

Intervention group (n=30): Oral L-theanine 200 mg daily plus methimazole for four weeks. Control group (n=30): Matching placebo plus methimazole for four weeks

Change in anxiety score measured using the GAD-7 questionnaire at baseline and after four weeks

In this study, 60 eligible patients will be randomly allocated in a 1:1 ratio to the intervention group (L-theanine plus methimazole) or the control group (placebo plus methimazole) after obtaining informed consent and completing the methimazole stabilization period. The unit of randomization will be the individual patient. Randomization will be performed using variable block sizes of 4 and 6. An independent individual, not involved in trial implementation, will generate the allocation sequence using computer-generated random numbers. Both the order of block sizes and treatment assignments within each block will be randomized. No stratification will be applied. According to the generated sequence, identical-appearing packages containing L-theanine or placebo will be prepared and sequentially numbered from 1 to 60. The principal investigator will be aware of the package contents but will not participate in patient enrollment or allocation. The research assistant responsible for enrollment and dispensing will assign the next sequentially numbered package only after confirming eligibility and obtaining informed consent. This assistant will have no access to the allocation sequence or package contents, thereby maintaining allocation concealment until assignment.

In this study, the principal investigator will be responsible for preparing the L-theanine supplement and the placebo, coding the packages for each group, and will be aware of the intervention type. The L-theanine supplement and placebo will be provided to a research associate in identical packages bearing specific codes, with no indication of the intervention type. This research associate will be responsible for delivering the packages to patients, collecting data, and assessing study outcomes, without knowledge of the package contents or the intervention assigned to the patients. Furthermore, the participants and the treating physician will remain unaware of whether the L-theanine supplement or the placebo is being administered. The codes corresponding to the intervention type will be retained by the principal investigator, and the allocation code will be disclosed only if medically necessary to ensure patient safety. Thus, blinding will be maintained for the participants, the treating physician, and the research associate responsible for intervention delivery, data collection, and outcome assessment, while the principal investigator remains aware of the group allocations.