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IRCT20100922004794N13 IRCT 2021-12-08 Dorsa Pharmaceutical Company Improvement in treatment of hypothyroidism using slow-release Liothyronine Randomized control Clinical Trial to assess the efficacy of the three different combined preparations of levothyroxine plus slow-release liothyronine 2022-02-20 anticipated 44 Complete https://irct.ir/trial/51700 interventional Randomization: Randomized, Blinding: Double blinded, Placebo: Not used, Assignment: Parallel, Purpose: Treatment, Other design features: The drug will be continued in three intervention groups (three combinations of Levothyroxine plus Liothyronine) and one control group (Levothyroxine monotherapy) for eight weeks. Patients will be visited at four-week intervals to measure TSH and assess therapy adherence and adverse effects. Drug dosage would be adjusted to maintain serum TSH concentration within 0.5-3 mU/l. Participants will be evaluated at baseline and one consequent follow-up at eight weeks. At first and last visit at eight weeks, venous blood samples will be collected from all participants after a 12-hour fast for measurement of serum TSH, total T3, total T4, free T4, FBS, total cholesterol, HDL cholesterol and triglycerides, insulin, LDH and CK, and metabolomics. ECG, resting heart rate, and BP will be measured, and all questionnaires will be filled out at the first and last visits (TSF and TSQ). Also, in the last visit, after blood sampling and getting the specified treatment at 8 am, the blood sampling will be done at 9 am, 10 am, 12 MD, 2 pm, 4 pm and the next day at 8 am, and serum levels of T4, FREE T4, TSH, and T3 will be measured in all samples to calculate T3/T4 ratio, T3 CMAX, and T3 TMAX and AUC (0-24). To ensure compliance with drug therapy, the responsible person will check the drug package and count the number of pill intake by direct questioning in 2 weeks intervals by phone call and pill counting at the last visit, Randomization description: Patients will be allocated to three intervention groups and one control group using stratified randomization. Six stratifications will be made based on age and gender. At first, patients will be assigned to three age groups of ≤50y, 51-70y, >70 y. Under each subgroup, patients will be assigned to male and female. Then under each sex subgroup, patients will be randomly assigned to four treatment groups using the random table, Blinding description: After implementation of randomization and specific coding, the subjects will be assigned to the groups using allocation concealment, which helps to keep clinicians, participants, and investigators unaware of upcoming assignments. The standard methods of ensuring allocation concealment will be sequentially numbered or coded opaque containers. For single-center clinical trials such as the current trial, we will identify a staff member not involved with the trial who can keep the randomization list. This staff will be instructed to keep the list private and only reveal a treatment allocation after receiving information demonstrating that the patient is eligible and has consented to the trial. The subjects and the investigators will be kept from knowing who will be assigned to which treatment (double-blind). Both groups will receive identical tablets in physical appearance, taste, and smell to fulfill this. 2 Hypothyroidism. Intervention 1: Intervention group 1: Taking 75µg LT4 Tab. plus 7.5µg SR-T3 Tab (ratio 1:10). Dorsa Pharmaceutical Company, Tavan Institute, will formulate these tablets. The patients will take medicine daily before breakfast for eight weeks. The treatment will be allocated based on the pre-specified random allocation. Intervention 2: Intervention group 2: Taking 68.5 µg LT4 Tab. plus 9 µg SR-T3 Tab (ratio 1:8). Dorsa Pharmaceutical Company, Tavan Institute, will formulate these tablets. The patients will take medicine daily before breakfast for eight weeks. The treatment will be allocated based on the pre-specified random allocation. Intervention 3: Intervention group 3: Taking 60 µg LT4 Tab. plus 12 µg SR-T3 Tab (ratio 1:5). Dorsa Pharmaceutical Company, Tavan Institute, will formulate these tablets. The patients will take medicine daily before breakfast for eight weeks. The treatment will be allocated based on the pre-specified random allocation. Intervention 4: Control group: Levothyroxine monotherapy Dorsa Pharmaceutical Company, Tavan Institute, will formulate these tablets. The patients will take medicine daily before breakfast for eight weeks. The treatment will be allocated based on the pre-specified random allocation. No - There is not a plan to make this available Justification or reason for not sharing IPD is These data are belonged to Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran
public Ladan Mehran
NO:23, Erabi St, Yaman St, Velenjak Ave
Tehran Iran (Islamic Republic of) 1985717413 +98 21 2243 2500 lmehran@endocrine.ac.ir Shahid Beheshti University of Medical Sciences scientific Ladan Mehran
No. 23, Erabi St, Yaman Ave, Velenjak
Tehran Iran (Islamic Republic of) 1985717413 +98 21 2243 2500 lmehran@endocrine.ac.ir Research Institute for Endocrine Sciences Iran (Islamic Republic of) Hypothyroid patients over 20 yrs. due to radioactive iodine intake for treating Graves’ Disease, who attained euthyroid status with LT4 monotherapy (TSH=0.5-5 mU/L is optimal). 20 years no limit Both Pregnancy, chronic kidney or liver disease, congestive heart failure, cancer, taking methimazole, PTU, Tamoxifen, estrogen, progesterone, and corticosteroids E03.9 Hypothyroidism, unspecified Treatment - Drugs Treatment - Drugs Treatment - Drugs Treatment - Drugs Intervention group 1: Taking 75µg LT4 Tab. plus 7.5µg SR-T3 Tab (ratio 1:10). Dorsa Pharmaceutical Company, Tavan Institute, will formulate these tablets. The patients will take medicine daily before breakfast for eight weeks. The treatment will be allocated based on the pre-specified random allocation. Intervention group 2: Taking 68.5 µg LT4 Tab. plus 9 µg SR-T3 Tab (ratio 1:8). Dorsa Pharmaceutical Company, Tavan Institute, will formulate these tablets. The patients will take medicine daily before breakfast for eight weeks. The treatment will be allocated based on the pre-specified random allocation. Intervention group 3: Taking 60 µg LT4 Tab. plus 12 µg SR-T3 Tab (ratio 1:5). Dorsa Pharmaceutical Company, Tavan Institute, will formulate these tablets. The patients will take medicine daily before breakfast for eight weeks. The treatment will be allocated based on the pre-specified random allocation. Control group: Levothyroxine monotherapy Dorsa Pharmaceutical Company, Tavan Institute, will formulate these tablets. The patients will take medicine daily before breakfast for eight weeks. The treatment will be allocated based on the pre-specified random allocation. T3/T4 ratio. Timepoint: 8 weeks after intervention. Method of measurement: Serum Total tri-iodothyronine(TT3), total thyroxine (TT4) will be determined on -20ºC stored serum samples by the electrochemiluminescence immunoassay (ECLIA) method, using Roche Diagnostics kits and Roche/Hitachi Cobas e-411 analyzer (GmbH, Mannheim, Germany). Serum TSH and Free T4 concentrations. Timepoint: At the baseline and end of the study. Method of measurement: On -20ºC stored serum samples by the electrochemiluminescence immunoassay (ECLIA) method, using Roche Diagnostics kits and Roche/Hitachi Cobas e-411 analyzer (GmbH, Mannheim, Germany). Serum Lipid Profile. Timepoint: At the baseline and end of the study. Method of measurement: Laboratory measurements with the related kits. FBS, LDH, CK, ferritin. Timepoint: At the baseline and end of the study. Method of measurement: Laboratory measurements with the related kits. Metabolomics. Timepoint: At the baseline and end of the study. Method of measurement: Laboratory measurements with the related kits. Cardiac parameters (ECG, resting heart rate, BP). Timepoint: At the baseline and end of the study. Method of measurement: Laboratory measurements with the related kits. Treatment satisfaction. Timepoint: At the first and last visits. Method of measurement: Treatment satisfaction questionnaire (THY-TSQ). Thyroid symptoms. Timepoint: At the first and last visits. Method of measurement: Thyroid symptom questionnaire. Dorsa Pharmaceutical Company Approved 2021-07-11 Ethics Human Research Review Committee of the Endocrine Research Center, Shahid Beheshti University no 23, Erabi St, Velenjak Tehran Tehran Iran (Islamic Republic of)