Comparison of Levothyroxine alone versus Levothyroxine plus Liothyronine in patients with persistent symptoms despite adequate thyroid hormone replacement

A prospective study exploring determinants of response to combination Levothyroxine Liothyronine (LT4+LT3) Therapy versus Levothyroxine Monotherapy in Symptomatic Hypothyroid patients with normal TSH Levels.

Status

Active, not recruiting

Phases

Phase 4

Study type

Interventional

Source

CTRI

Registry ID

CTRI/2026/02/104745

Enrollment

Registered

2026-02-25

Start date

Unknown

Completion date

Unknown

Last updated

2026-03-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Health Condition 1: E038- Other specified hypothyroidism

Interventions

Intervention1: Combination of Levothyroxine and Liothyronine arm: Route- Oral Frequency- Levothyroxine once a day and Liothyronine twice a day Duration of treatment 3 months Replacing the dose the pat

Eligibility

Inclusion criteria

Inclusion criteria: Normal serum TSH ThyPRO 39 score more than 32 On stable LT4 dose for more than or equal to 3 months Adequate replacement more than or equal to 6 months

Exclusion criteria

Exclusion criteria: Diabetes mellitus with a HbA1c more than 7 percent Serious systemic illness or malignancy Overt autoimmune disease Fibromyalgia Chronic fatigue Drugs influencing thyroid function, pregnancy, or hormonal contraceptive use.

Design outcomes

Primary

Measure	Time frame
To compare the effect of combination levothyroxine liothyronine (LT4+LT3) therapy versus levothyroxine (LT4) monotherapy on thyroid-related quality of life (assessed by the ThyPRO-39 questionnaire) in symptomatic hypothyroid patients with normal TSH levels.Timepoint: Baseline 3 months	—

Secondary

Measure	Time frame
To evaluate the effects of LT4+LT3 combination therapy compared to LT4 monotherapy on thyroid-related biochemical parameters including serum lipid profile, sex hormone binding globulin (SHBG), and the fT3/fT4 ratio and on thyroid hormone sensitivity as measured by the Thyroid Feedback Quantile-based Index (TFQI).Timepoint: 3 months;To determine correlations between improvements in quality-of-life scores and changes in biochemical markers of thyroid hormone action (fT3/fT4 ratio, SHBG, lipid profile, and Thyroid hormone sensitivity index [Thyroid Feedback Quantile-based Index- TFQI]) following combination therapy, and to identify potential serum biomarkers that may serve as surrogate indicators of tissue-level thyroid hormone activity for guiding individualized thyroid hormone replacement strategiesTimepoint: 3 months;To evaluate whether baseline TFQI can predict clinical and biochemical response to LT4+LT3 therapy, thereby identifying patient subgroups most likely to benefit from combination treatment. Timepoint: 3 months	—

Measure

Time frame

To evaluate the effects of LT4+LT3 combination therapy compared to LT4 monotherapy on thyroid-related biochemical parameters including serum lipid profile, sex hormone binding globulin (SHBG), and the fT3/fT4 ratio and on thyroid hormone sensitivity as measured by the Thyroid Feedback Quantile-based Index (TFQI).Timepoint: 3 months;To determine correlations between improvements in quality-of-life scores and changes in biochemical markers of thyroid hormone action (fT3/fT4 ratio, SHBG, lipid profile, and Thyroid hormone sensitivity index [Thyroid Feedback Quantile-based Index- TFQI]) following combination therapy, and to identify potential serum biomarkers that may serve as surrogate indicators of tissue-level thyroid hormone activity for guiding individualized thyroid hormone replacement strategiesTimepoint: 3 months;To evaluate whether baseline TFQI can predict clinical and biochemical response to LT4+LT3 therapy, thereby identifying patient subgroups most likely to benefit from combination treatment. Timepoint: 3 months

—

Countries

India

Contacts

Public ContactDr Sonali Appaiah

St. Johns Medical College and Hospital

sonaliappaiah2@gmail.com9448490363

Outcome results

None listed

Source: CTRI (via WHO ICTRP) · Data processed: Mar 14, 2026