HypothyroidismPhase 2/3NCT06731764
Novel Approaches to the Treatment of Hypothyroidism
A Phase 2/3 study testing Levothyroxine, Levothyroxine/Liothyronine once daily and Levothyroxine/Liothyronine twice daily in people with Hypothyroidism, run by UConn Health at 1 site in United States.
Trial summary
Hypothyroidism is a common condition, more frequent in females, associated with excess of cardiovascular risk and poor quality of life not completely abrogated by treatment with levothyroxine. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypothyroidism
- What is being tested?
- Levothyroxine, Levothyroxine/Liothyronine once daily and Levothyroxine/Liothyronine twice daily
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Dec 2024to 30 Jun 2028
- Phase
- Phase 2/3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- History of hypothyroidism Treatment with levothyroxine Levothyroxine dose >1.2 mcg/kg
Who cannot join
- Body weight <50 or >100 Kg.
- Indication for TSH suppression (high risk follicular-derived thyroid cancer).
- Secondary (pituitary) hypothyroidism (ICD-10 E23.0); Pregnancy; breastfeeding; uncontrolled diabetes (HbA1c >8.5% at screening); use of oral Semaglutide (Rybelsus); Uncontrolled Hypertension (BP > 140/90 at screening); current use of T3-containing therapies (Liothyronine, desiccated thyroid extracts).
- Patients receiving lipid-lowering therapies must maintain the same dose throughout the participation in the study. Changes in lipid lowering therapy/dose will result in termination from the study.
- Patients receiving anti-acid (H2 blockers, proton pump inhibitors) therapies must maintain the same dose throughout the participation in the study. Changes in anti-acid therapy/dose will result in termination from the study. Use of other medications known to interfere with the absorption of thyroid hormone, or affecting the thyroid hormone axis (Burch 2019) will be considered exclusion criteria.
- Bariatric surgery, initiation of GLP-1 agonist therapy (irrespective of the indication), enrollment in structured weight loss programs will result in dismissal from the study.
- Current pregnancy, pregnancy planned within the next 6 months, and lack of contraception in women of reproductive age will be exclusionary. We will verify that the participant is not pregnant through a urine pregnancy test at the time of the first study visit and at each of the follow-up visits. Any participants who become pregnant will terminate the study.
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, 1 recruiting
- Recruiting
UConn Health
Farmington, Connecticut, 06030
Nicole Glidden, (860) 679-4647, DOMClinicalResearch@uchc.edu
Jenny Derouen, (860) 679-4647, DOMClinicalResearch@uchc.edu
About this study
Hypothyroidism is a common condition, more frequent in females, associated with excess of cardiovascular risk and poor quality of life not completely abrogated by treatment with levothyroxine.
There is an unmet need to define a safe, effective, and feasible regimen to be applied in large trials aimed at assessing levothyroxine/liothyronine combination therapy in patients living with hypothyroidism.
To address this knowledge gap we propose a randomized, three-arm, double-blind, controlled, escalating dose parallel pilot study whose results will lay the foundation of large multicenter trial(s) able to demonstrate the effectiveness (or lack thereof) of levothyroxine/liothyronine combination therapy.
Read the detailed description
Hypothyroidism is a common condition associated with excess of cardiovascular risk and poor quality of life which are not completely abrogated by treatment with levothyroxine (synthetic T4, LT4), potentially because of the inability to compensate for the loss of T3 secreted by the thyroid gland. Experimental data in animal models indicate that only combination LT4 and liothyronine (synthetic T3, LT3) can restore normal concentrations of thyroid hormones across the tissues target of the hormonal action. Clinical trials based on LT4/LT3 combination therapy and desiccated thyroid extracts (containing T3) have provided conflicting data, but the plurality of the results indicates a preference toward T3-containing therapies when compared to LT4 alone. Conversely, the short half-life of T3 poses concern of cardiovascular toxicity due to fluctuating levels of T3, particularly when LT3 is prescribed in single dose. No study has systematically assessed the optimal dose and frequency of LT3 administration in LT4/LT3 combination therapy. There is an unmet need to define a safe, effective, and feasible regimen to be applied in large trials aimed at assessing LT4/LT3 therapy efficacy and safety.
We have conducted clinical studies aimed at characterizing the pharmacokinetics and pharmacodynamics of LT3 and, more recently, we completed a R21-sponsored LT4/LT3 combination therapy clinical trial in patients undergoing total thyroidectomy. The data suggest that LT4/LT3 combination therapy is effective in normalizing thyroid hormone levels and in preventing the rise in serum cholesterol and weight when compared to LT4 alone. Moreover, our results from a prior study appear to negate a clinical role of rapid T3 action, supporting the use of LT3 in single administration. These original findings serve as foundation for the current proposal.
Hypothesis: A once daily administration of LT4/LT3 combination therapy will be (i) effective yet safe, (ii) comparable to a twice daily LT4/LT3 administration regimen, and (iii) superior to LT4 therapy in improving clinically relevant indices of thyroid hormone action.
To test this hypothesis, we propose a randomized, three-arm, double-blind, controlled, escalating dose parallel pilot study in which 90 patients with hypothyroidism (30 each group) will be randomized to six months of treatment with LT4, LT4/LT3 with LT3 once daily, or LT4/LT3 with LT3 twice daily.
This novel and rigorous study based on our original observations will fill the knowledge gap of effects and dosing of LT4/LT3 combination therapy, laying the foundation for large multicenter trial(s) able to demonstrate the effectiveness (or lack thereof) of LT4/LT3 combination therapy, fulfilling the aims of PAS-23-086.
- Conditions
- Hypothyroidism
- Being tested
- Levothyroxine, Levothyroxine/Liothyronine once daily, Levothyroxine/Liothyronine twice daily
- Medical subject headings
- Hypothyroidism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LevothyroxineDrug
Also called LT4
Patients will receive Levothyroxine/Placebo
Levothyroxine/Liothyronine with Liothyronine administered twice daily.
Levothyroxine/Liothyronine once dailyDrug
Also called LT4/LT3
Patients will receive Levothyroxine/Liothyronine with Liothyronine administered once daily;
Levothyroxine/Liothyronine twice dailyDrug
Also called LT4/LT3
Patients will receive Levothyroxine/Liothyronine with Liothyronine administered twice daily;
| Study group | Role | What they receive |
|---|---|---|
| Levothyroxine alone | Active comparator | Patients in this arm will be administered Levothyroxine/Placebo Receives: Drug: Levothyroxine |
| Combination therapy liothyronine once daily | Experimental | Patients in the arm will be administered Levothyroxine/Liothyronine with Liothyronine administered once daily plus placebo Receives: Drug: Levothyroxine; Drug: Levothyroxine/Liothyronine once daily |
| Combination therapy liothyronine twice daily | Experimental | Patients in this arm will be administered Levothyroxine/Liothyronine with Liothyronine administered twice daily. Receives: Drug: Levothyroxine; Drug: Levothyroxine/Liothyronine twice daily |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Total Cholesterol
Changes between groups
Measured: 6 month
Changes in LDL Cholesterol
Changes between groups
Measured: 6 month
Secondary outcomes (1)
Changes in Weight
Changes between groups
Measured: 6 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2024
- Study start10 Dec 2024
- Primary completion31 Dec 2027 (estimated)
- Study completion30 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypothyroidismStudies of the same condition, open and under way.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- UConn Health
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Francesco Celi, UConn Health
- Investigators
- Francesco Celi, Principal investigator, UConn Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06731764
- Sponsor's protocol ID
- 24-186-1
- Status last verified
- Mar 2026
- First submitted
- 9 Dec 2024
- Last updated
- 19 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Novel Approaches to the Treatment of Hypothyroidism
- ClinicalTrials.gov ID
- NCT06731764
- Acronym / sponsor ID
- 24-186-1
- Conditions
- Hypothyroidism
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- UConn HealthUniversity, hospital or other
- Study start
- 10 Dec 2024 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 30 Jun 2028 (estimated)
- First posted
- 12 Dec 2024 (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.
Hypothyroidism is a common condition, more frequent in females, associated with excess of cardiovascular risk and poor quality of life not completely abrogated by treatment with levothyroxine.
There is an unmet need to define a safe, effective, and feasible regimen to be applied in large trials aimed at assessing levothyroxine/liothyronine combination therapy in patients living with hypothyroidism.
To address this knowledge gap we propose a randomized, three-arm, double-blind, controlled, escalating dose parallel pilot study whose results will lay the foundation of large multicenter trial(s) able to demonstrate the effectiveness (or lack thereof) of levothyroxine/liothyronine combination therapy.
Detailed description
Hypothyroidism is a common condition associated with excess of cardiovascular risk and poor quality of life which are not completely abrogated by treatment with levothyroxine (synthetic T4, LT4), potentially because of the inability to compensate for the loss of T3 secreted by the thyroid gland. Experimental data in animal models indicate that only combination LT4 and liothyronine (synthetic T3, LT3) can restore normal concentrations of thyroid hormones across the tissues target of the hormonal action. Clinical trials based on LT4/LT3 combination therapy and desiccated thyroid extracts (containing T3) have provided conflicting data, but the plurality of the results indicates a preference toward T3-containing therapies when compared to LT4 alone. Conversely, the short half-life of T3 poses concern of cardiovascular toxicity due to fluctuating levels of T3, particularly when LT3 is prescribed in single dose. No study has systematically assessed the optimal dose and frequency of LT3 administration in LT4/LT3 combination therapy. There is an unmet need to define a safe, effective, and feasible regimen to be applied in large trials aimed at assessing LT4/LT3 therapy efficacy and safety.
We have conducted clinical studies aimed at characterizing the pharmacokinetics and pharmacodynamics of LT3 and, more recently, we completed a R21-sponsored LT4/LT3 combination therapy clinical trial in patients undergoing total thyroidectomy. The data suggest that LT4/LT3 combination therapy is effective in normalizing thyroid hormone levels and in preventing the rise in serum cholesterol and weight when compared to LT4 alone. Moreover, our results from a prior study appear to negate a clinical role of rapid T3 action, supporting the use of LT3 in single administration. These original findings serve as foundation for the current proposal.
Hypothesis: A once daily administration of LT4/LT3 combination therapy will be (i) effective yet safe, (ii) comparable to a twice daily LT4/LT3 administration regimen, and (iii) superior to LT4 therapy in improving clinically relevant indices of thyroid hormone action.
To test this hypothesis, we propose a randomized, three-arm, double-blind, controlled, escalating dose parallel pilot study in which 90 patients with hypothyroidism (30 each group) will be randomized to six months of treatment with LT4, LT4/LT3 with LT3 once daily, or LT4/LT3 with LT3 twice daily.
This novel and rigorous study based on our original observations will fill the knowledge gap of effects and dosing of LT4/LT3 combination therapy, laying the foundation for large multicenter trial(s) able to demonstrate the effectiveness (or lack thereof) of LT4/LT3 combination therapy, fulfilling the aims of PAS-23-086.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Levothyroxine alone | Active comparator | Drug: LevothyroxinePatients in this arm will be administered Levothyroxine/Placebo |
| Combination therapy liothyronine once daily | Experimental | Drug: Levothyroxine, Drug: Levothyroxine/Liothyronine once dailyPatients in the arm will be administered Levothyroxine/Liothyronine with Liothyronine administered once daily plus placebo |
| Combination therapy liothyronine twice daily | Experimental | Drug: Levothyroxine, Drug: Levothyroxine/Liothyronine twice dailyPatients in this arm will be administered Levothyroxine/Liothyronine with Liothyronine administered twice daily. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- History of hypothyroidism Treatment with levothyroxine Levothyroxine dose >1.2 mcg/kg
Key exclusion criteria (7 listed)
- Body weight <50 or >100 Kg.
- Indication for TSH suppression (high risk follicular-derived thyroid cancer).
- Secondary (pituitary) hypothyroidism (ICD-10 E23.0); Pregnancy; breastfeeding; uncontrolled diabetes (HbA1c >8.5% at screening); use of oral Semaglutide (Rybelsus); Uncontrolled Hypertension (BP > 140/90 at screening); current use of T3-containing therapies (Liothyronine, desiccated thyroid extracts).
- Patients receiving lipid-lowering therapies must maintain the same dose throughout the participation in the study. Changes in lipid lowering therapy/dose will result in termination from the study.
- Patients receiving anti-acid (H2 blockers, proton pump inhibitors) therapies must maintain the same dose throughout the participation in the study. Changes in anti-acid therapy/dose will result in termination from the study. Use of other medications known to interfere with the absorption of thyroid hormone, or affecting the thyroid hormone axis (Burch 2019) will be considered exclusion criteria.
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 |
|---|---|---|
| LevothyroxineAlso: LT4Patients will receive Levothyroxine/Placebo Levothyroxine/Liothyronine with Liothyronine administered twice daily. | Drug | Combination therapy liothyronine once daily, Combination therapy liothyronine twice daily, Levothyroxine alone |
| Levothyroxine/Liothyronine once dailyAlso: LT4/LT3Patients will receive Levothyroxine/Liothyronine with Liothyronine administered once daily; | Drug | Combination therapy liothyronine once daily |
| Levothyroxine/Liothyronine twice dailyAlso: LT4/LT3Patients will receive Levothyroxine/Liothyronine with Liothyronine administered twice daily; | Drug | Combination therapy liothyronine twice daily |
Primary outcome
Changes in Total Cholesterol
Time frame: 6 month
Changes between groups
Changes in LDL Cholesterol
Time frame: 6 month
Changes between groups
1 secondary outcome
Changes in Weight
Time frame: 6 month
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 19 Mar 2026.
- Individual participant dataSharing planned: No
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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.
Francesco Celi principal investigator
UConn Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Levothyroxine, Levothyroxine/Liothyronine once daily and Levothyroxine/Liothyronine twice daily in people with Hypothyroidism, run by UConn Health 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 1 inclusion and 7 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: looking for participants now, as of the sponsor's last update on 19 Mar 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 combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Francesco S Celi, MD, MHSc. ((860) 679-2715, celi@uchc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in Total Cholesterol (time frame: 6 month). The study lists 2 primary outcomes in all. 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 19 Mar 2026.