Evaluation of the effect of adding vitamin C supplementation to Levothyroxine compared with Levothyroxine alone on laboratory parameters and clinical symptoms in patients with primary hypothyroidism: A randomized, placebo-controlled pilot clinical trial

Investigating the effect of adding a Vitamin C supplement (60 mg) to levothyroxine, compared to levothyroxine alone, on laboratory parameters and clinical symptoms in patients with primary hypothyroidism

This study is a Phase ‌3, randomized, double-blind, placebo-controlled clinical trial with a two-group parallel design, conducted on 40 patients. Randomization will be performed using fixed-size blocks of 2 and Excel software.

This study will be conducted at specialized endocrinology clinics affiliated with the Islamic Azad University of Medical Sciences, Tehran. After providing informed consent, eligible patients will be randomly assigned to either the Vitamin C group or the placebo group, and the intervention will continue for eight weeks. Clinical and laboratory assessments will be performed at the beginning and end of the study.

Inclusion criteria: Diagnosis of primary hypothyroidism by a specialist, based on elevated TSH accompanied by low or low-normal free T4 (FT4) levels. TSH levels exceeding the laboratory's upper limit of normal and above 4.5 mIU/L in a recent test, despite regular levothyroxine intake. Exclusion criteria: Chronic kidney disease (e.g., eGFR < 60 ml/min/1.73m² or CKD stage 3 or higher). History of recurrent calcium kidney stones. Known G6PD deficiency.

Intervention group: Patients with primary hypothyroidism who receive 60 mg Vitamin C effervescent tablet daily for 8 weeks. Control group: Patients with primary hypothyroidism who receive placebo effervescent tablet daily for 8 weeks.

TSH level – Free T4 level – Zulewski questionnaire score

Participants will be randomly assigned to either the intervention group (Vitamin C) or the control group (placebo) in a 1:1 ratio. A fixed-block randomization method (block size of 2) will be employed to ensure an even distribution of participants across the treatment groups throughout the enrollment period. The randomization sequence will be generated by an independent third party—who is not involved in participant assessment or data collection—using randomization software (such as Sealedenvelope.com). The allocation sequence within each block will be fully randomized, and the list contents will remain concealed from the research team until the study concludes (allocation concealment). Following the acquisition of informed consent and confirmation of eligibility criteria, participants will be assigned to one of two groups based on their sequential number in a coded list, in the order of their enrollment. The person responsible for allocation—unaware of the contents of the subsequent block—will determine and announce the assigned group solely based on the participant's sequential number. This process enables the control of selection bias and the maintenance of statistical balance between the groups.

The patient, physician, researcher, and evaluator (student) will remain unaware of whether the patient has received the drug or the placebo (double-blinding). The drug (Vitamin C) and the placebo will be prepared as effervescent tablets that are identical in shape, color, size, taste, and method of administration, ensuring that participants cannot distinguish between them. The coding of the medication boxes will be performed by an independent third party not involved in the study, and the code will not be broken until the study concludes.

All study data will be available for sharing upon request after de-identification and anonymization of participant information, in accordance with confidentiality requirements.

Just after the article's publication

To whom data/document is available

De-identified individual data will be available to qualified researchers upon written request and ethics committee approval after publication of the main results. Data may only be used for scientific purposes; commercial use is prohibited.

For further information or to request access to the data, applicants may correspond via email with the Clinical Department of the Islamic Azad University (Pharmaceutical Sciences Branch) and Dr. Hashemian. Email: farshadhashemian@gmail.com

Applicants may request access to the study data by contacting the relevant department through the provided email address or telephone number. Requests should include information regarding the applicant’s academic background, institutional affiliation, and the intended purpose of data use. Applicants will also be required to acknowledge and appropriately cite the original study in any resulting scientific work. De-identified study data will be available beginning six months after publication of the study results. Following approval of the request by the principal investigator, the data files will be provided to eligible applicants via email within approximately one week.