T4/T3 Therapy in Hypothyroidism

NCT07424183 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 10094647R01DK137207
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This study will test whether 6 months of combination therapy with levothyroxine (LT4) plus liothyronine (LT3) is superior to LT4 plus placebo in participants with hypothyroidism who have residual symptoms of hypothyroidism with TSH levels within the reference range.

Conditions

Hypothyroidism Primary

Keywords

Hypothyroidism; levothyroxine; liothyronine

Outcome Measures

Primary Outcomes (1)

• ThyPRO Composite QOL Scale

  22 items, scored 0-100, higher scores indicate worse status

  6 months

Secondary Outcomes (10)

• ThyPRO subscales

  6 months

• Thyroid Symptoms Questionnaire (TSQ)

  6 months

• Cognitive measures

  Baseline and 6 months

• Beck Depression Inventory

  Baseline and 6 months

• Beck Anxiety Inventory

  Baseline and 6 months

Other Outcomes (1)

• Symptom checks

  Weekly for 8 weeks and at months 3, 4, and 5

Study Arms (2)

LT4+LT3

EXPERIMENTAL

Levothyroxine plus liothyronine therapy

Drug: Liothyronine (L-T3); Drug: Levothyroxine Sodium (LT4) Tablets

LT4+placebo

ACTIVE COMPARATOR

Levothyroxine plus liothyronine placebo

Drug: Levothyroxine Sodium (LT4) Tablets; Drug: Liothyronine (LT3) placebo

Interventions

Liothyronine (L-T3) DRUG

Participants will either take LT3 with an LT4 dose that is reduced from baseline or they will take liothyronine placebo with their baseline LT4 dose.

LT4+LT3

Levothyroxine Sodium (LT4) Tablets DRUG

All participants will take levothyroxine.

LT4+LT3; LT4+placebo

Liothyronine (LT3) placebo DRUG

Identical placebo tablet without containing liothyronine

LT4+placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, aged 18-70 years
• Hypothyroidism due to either thyroid failure or total thyroidectomy for structural thyroid disease (nodules, benign goiter, or thyroid cancer) for at least 6 months
• Taking 75-150 mcg per day LT4 and a minimum of 1.2 mcg/kg/day, with stable dose of LT4 for at least 3 months prior to enrollment
• TSH of 0.5 to 4.0 mU/L within 2 months of enrollment
• Persistent symptoms for at least 2 months, and a TSQ score of ≥ 5
• For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 4 weeks after the end of study intervention.

You may not qualify if:

• Current use of LT3, thyroid extracts, Tirosint liquid or capsules, amiodarone, lithium, methimazole, propylthiouracil, supraphysiologic doses of corticosteroids, immunotherapy, tyrosine kinase inhibitors, interferon, or biotin supplements
• Diseases of the pituitary or hypothalamus
• History of thyroid cancer requiring suppression of TSH secretion
• Unstable cardiac conditions, including uncontrolled hypertension (current blood pressure greater than 160/100), arrhythmia, or angina
• Uncontrolled psychiatric disorders
• Pregnancy or lactation, or planned pregnancy within the next 7 months
• History of food dye allergies
• GFR \<30 ml/min/1.73 m2
• Other conditions which, in the opinion of the investigators, would prevent them from participating in the full duration of the study (for example, end-stage cancer)

Sponsors & Collaborators

• University of Pennsylvania: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Penn Medicine, Smilow Center for Translational Resarch,

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Hypothyroidism

Interventions

Triiodothyronine; Thyroxine; Tablets

Condition Hierarchy (Ancestors)

Thyroid Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Thyronines; Thyroid Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Dosage Forms; Pharmaceutical Preparations

Central Study Contacts

Anne R. Cappola, MD, ScM

CONTACT

215-573-5359; acappola@pennmedicine.upenn.edu

Theresa Scattergood, MSN, RN

CONTACT

215-898-5664; theresa.scattergood@pennmedicine.upenn.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: February 6, 2026
• First Posted: February 20, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (1)