Hypothyroidism PrimaryPhase 2NCT07424183
T4/T3 Therapy in Hypothyroidism
A Phase 2 study testing Liothyronine (L-T3) and Levothyroxine Sodium (LT4) Tablets in people with Hypothyroidism Primary, run by University of Pennsylvania at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hypothyroidism Primary
- What is being tested?
- Liothyronine (L-T3) and Levothyroxine Sodium (LT4) Tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2026to Nov 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 9Show fewer
- 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)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Penn Medicine, Smilow Center for Translational Resarch,
Philadelphia, Pennsylvania, 19104
About this study
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.
Read the detailed description
.Participants will
- Take LT4+LT3 or LT4+placebo for 6 months
- Visit the clinic at the beginning and the end of the study for a blood test and to answer questionnaires.
- Have blood tests checked at 6 and 13 weeks and symptom checks by text (weekly to monthly)
- Conditions
- Hypothyroidism Primary
- Being tested
- Liothyronine (L-T3), Levothyroxine Sodium (LT4) Tablets, Liothyronine (LT3) placebo
- Keywords
- Hypothyroidism, levothyroxine, liothyronine
- Medical subject headings
- Hypothyroidism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
Levothyroxine Sodium (LT4) TabletsDrug
All participants will take levothyroxine.
Liothyronine (LT3) placeboDrug
Identical placebo tablet without containing liothyronine
| Study group | Role | What they receive |
|---|---|---|
| LT4+LT3 | Experimental | Levothyroxine plus liothyronine therapy Receives: Drug: Liothyronine (L-T3); Drug: Levothyroxine Sodium (LT4) Tablets |
| LT4+placebo | Active comparator | Levothyroxine plus liothyronine placebo Receives: Drug: Levothyroxine Sodium (LT4) Tablets; Drug: Liothyronine (LT3) placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
ThyPRO Composite QOL Scale
22 items, scored 0-100, higher scores indicate worse status
Measured: 6 months
Secondary outcomes (10)
ThyPRO subscales
ThyPRO hypothyroid symptoms and tiredness subscales, 4 items, scored 0-100, higher scores indicate worse status
Measured: 6 months
Thyroid Symptoms Questionnaire (TSQ)
Thyroid symptoms scale, 12 items, score range 0-36, higher score indicates worse status
Measured: 6 months
Cognitive measures
NIH Toolbox Fluid Cognition Score, based around median of 100, higher scores indicate higher function
Measured: Baseline and 6 months
Beck Depression Inventory
21 items, range of 0-63, higher scores indicate more depressive symptoms
Measured: Baseline and 6 months
Beck Anxiety Inventory
21 items, range 0-63, higher scores indicate more anxiety
Measured: Baseline and 6 months
Pittsburgh Sleep Quality Index
19 items, range of 0-21, higher scores indicate worse sleep
Measured: 6 months
Weight
Kilograms
Measured: 6 months
LDL cholesterol
Blood test, g/dL
Measured: 6 months
Serum c-telopeptide
Blood test, pg/mL
Measured: 6 months
Satisfaction with randomized status
Participants will be asked if they can guess their randomization status and satisfaction with randomized status
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2026
- Study startNov 2026 (estimated)
- Primary completionNov 2027 (estimated)
- Study completionNov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hypothyroidism PrimaryStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Anne Cappola, MD, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07424183
- Sponsor's protocol ID
- 10094647
- Other IDs
- R01DK137207
- Status last verified
- Aug 2026
- First submitted
- 6 Feb 2026
- Last updated
- 20 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- T4/T3 Therapy in Hypothyroidism
- ClinicalTrials.gov ID
- NCT07424183
- Acronym / sponsor ID
- 10094647
- Conditions
- Hypothyroidism Primary
- Keywords
- Hypothyroidism, levothyroxine, liothyronine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Nov 2026 (estimated)
- Primary completion
- Nov 2027 (estimated)
- Study completion
- Nov 2027 (estimated)
- First posted
- 20 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
.Participants will
- Take LT4+LT3 or LT4+placebo for 6 months
- Visit the clinic at the beginning and the end of the study for a blood test and to answer questionnaires.
- Have blood tests checked at 6 and 13 weeks and symptom checks by text (weekly to monthly)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LT4+LT3 | Experimental | Drug: Liothyronine (L-T3), Drug: Levothyroxine Sodium (LT4) TabletsLevothyroxine plus liothyronine therapy |
| LT4+placebo | Active comparator | Drug: Levothyroxine Sodium (LT4) Tablets, Drug: Liothyronine (LT3) placeboLevothyroxine plus liothyronine placebo |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Liothyronine (L-T3)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. | Drug | LT4+LT3 |
| Levothyroxine Sodium (LT4) TabletsAll participants will take levothyroxine. | Drug | LT4+LT3, LT4+placebo |
| Liothyronine (LT3) placeboIdentical placebo tablet without containing liothyronine | Drug | LT4+placebo |
Primary outcome
ThyPRO Composite QOL Scale
Time frame: 6 months
22 items, scored 0-100, higher scores indicate worse status
10 secondary outcomes
ThyPRO subscales
Time frame: 6 months
Thyroid Symptoms Questionnaire (TSQ)
Time frame: 6 months
Cognitive measures
Time frame: Baseline and 6 months
Beck Depression Inventory
Time frame: Baseline and 6 months
Beck Anxiety Inventory
Time frame: Baseline and 6 months
Pittsburgh Sleep Quality Index
Time frame: 6 months
Weight
Time frame: 6 months
LDL cholesterol
Time frame: 6 months
Serum c-telopeptide
Time frame: 6 months
Satisfaction with randomized status
Time frame: 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2026.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Liothyronine (L-T3) and Levothyroxine Sodium (LT4) Tablets in people with Hypothyroidism Primary, run by University of Pennsylvania at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 20 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Anne R. Cappola, MD, ScM (215-573-5359, acappola@pennmedicine.upenn.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ThyPRO Composite QOL Scale (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2026.