T3 Instillation for Acute Respiratory Distress Syndrome

(ARDS+T3 Trial)

Recruiting at 4 trial locations

Overseen By David Ingbar, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Minnesota

Disqualifiers: Thyroid cancer, Hyperthyroidism, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 5 days

68 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for patients with Acute Respiratory Distress Syndrome (ARDS), a serious lung condition that makes breathing difficult. The trial will explore whether Liothyronine Sodium (T3), when placed directly into the lungs, can help clear lung fluid and reduce inflammation, thereby improving breathing. Participants will receive either this new treatment or standard care for comparison. The trial seeks individuals in intensive care on ventilators with ARDS symptoms, such as recent lung issues and difficulty breathing not caused by heart problems. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that Liothyronine Sodium (T3) is likely to be safe for humans?

Research has shown that Liothyronine Sodium (T3), used in a special form for breathing treatments, has been studied for safety and tolerability. Early laboratory studies have led to further human trials, suggesting the treatment is generally safe. However, medical guidelines highlight that high blood levels of T3 could pose a safety concern. Trials carefully monitor these levels to ensure participant safety. The study's Phase 2 status indicates that earlier stages likely demonstrated sufficient safety to warrant testing with more participants. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Acute Respiratory Distress Syndrome (ARDS), which typically involve mechanical ventilation and supportive care, Liothyronine Sodium (T3) is unique because it's administered directly into the airways. This new delivery method allows for targeted action right where it's needed – in the lungs. Researchers are excited about T3 because it could potentially enhance lung function more effectively by using this localized approach, possibly leading to faster improvement in respiratory conditions.

What evidence suggests that Liothyronine Sodium (T3) might be an effective treatment for ARDS?

Research suggests that Liothyronine Sodium (T3) might help treat Acute Respiratory Distress Syndrome (ARDS) by improving lung function. Early animal studies showed that T3 helped clear excess fluid from the lungs, potentially leading to better blood oxygen levels. In this trial, participants in the treatment arm will receive a modified formulation of T3 specifically for airway instillation. The treatment aims to reduce lung swelling, a major issue in ARDS. Although detailed information from human studies remains limited, early results are promising and suggest that T3 could improve breathing for people with ARDS. ^{1 2 3 6 7}

Who Is on the Research Team?

David H Ingbar, MD

Principal Investigator

University of Minnesota

Timothy P Rich, MD

Principal Investigator

University of Minnesota

Ronald A Reikoff, MD

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

This trial is for adults over 18 with ARDS needing ventilators in ICU. They must be able to consent or have a representative who can, and not be pregnant or breastfeeding. Excluded are those allergic to the drug, with thyroid cancer, hyperthyroidism, significant heart disease, or unlikely to follow the study through.

Inclusion Criteria

I am not pregnant.

I can give my consent or have someone legally authorized to do so on my behalf.

I am in the ICU and need a machine to help me breathe due to severe lung injury.

Exclusion Criteria

Known allergy to study drug.

Inadequate medical history for determining inclusion/exclusion criteria, as determined by the Principal Investigator and/or Sub- Investigators.

Unlikely to complete the protocol with clinic follow-up after discharge, as determined by the Principal Investigator and/or Sub- Investigators or hospice status.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive Liothyronine Sodium (T3) instilled into the airway twice daily for 5 days or until extubation

5 days

Daily monitoring during treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment, including oxygenation indices and cardiovascular events

120 hours post-dose

What Are the Treatments Tested in This Trial?

Interventions

• Liothyronine Sodium (T3)

Trial Overview The trial tests if Liothyronine Sodium (T3), instilled directly into the lungs of ARDS patients, is safe and effective at improving lung function by increasing fluid clearance and reducing inflammation as measured by oxygenation levels.

How Is the Trial Designed?

Group I: Treatment Arm Experimental Treatment 1 Intervention

Liothyronine Sodium (T3+0.9% sodium chloride) modified formulation specifically for airway instillation.

Group II: Control arm Experimental Treatment 1 Intervention

Standard of Care

Liothyronine Sodium (T3) is already approved in United States, European Union for the following indications:

Approved in United States as Cytomel for:

• Hypothyroidism
• Myxedema coma
• Thyroid suppression test
• TSH suppression
• Underactive thyroid

Approved in European Union as Tertroxin for:

• Hypothyroidism
• Myxedema coma

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Published Research Related to This Trial

In a study of six male subjects with primary hypothyroidism, serum levels of T4 and T3 decreased while rT3 increased during hospitalization for acute illness, but returned to normal levels shortly after discharge.

The transient changes in thyroid hormone levels and TSH suggest that healthcare providers should avoid making frequent adjustments to Levothyroxine (LT4) doses during acute illnesses, as these fluctuations are similar to those seen in healthy individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thyroid hormone indices during illness in six hypothyroid subjects rendered euthyroid with levothyroxine therapy. Wadwekar, D., Kabadi, UM.[2015]

A reformulated version of the thyroid hormone T3, when administered intratracheally in a safe dose, showed no significant adverse effects in a preclinical study with healthy rats, paving the way for future clinical trials.

This study supports the initiation of a phase I/II clinical trial to evaluate the safety and tolerability of T3 in patients with acute respiratory distress syndrome (ARDS), including those affected by COVID-19, highlighting its potential as a treatment for pulmonary edema.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Preclinical Safety Study of Thyroid Hormone Instilled into the Lungs of Healthy Rats-an Investigational Therapy for ARDS. Flory, CM., Norris, BJ., Larson, NA., et al.[2021]

In a study of patients with hypothyroidism switching from levothyroxine to liothyronine, once-daily liothyronine administration resulted in significant fluctuations in serum T3 levels, with peak concentrations reaching 292.8 ng/dL after dosing.

Despite the increase in T3 levels, serum TSH did not return to baseline levels seen with levothyroxine therapy, indicating that liothyronine monotherapy may not fully replicate the hormonal balance achieved with levothyroxine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daily Administration of Short-Acting Liothyronine Is Associated with Significant Triiodothyronine Excursions and Fails to Alter Thyroid-Responsive Parameters. Jonklaas, J., Burman, KD.[2022]

Three cases of myxedema coma were successfully treated with I-triiodothyronine (T3) administered either nasogastrically or intravenously, highlighting the efficacy of T3 in rapidly correcting severe hypothyroidism symptoms in critically ill patients.

In cases where oral T3 was not absorbed due to intestinal issues, intravenous T3 was effective in restoring metabolic function, while oral thyroxine (T4) alone was insufficient to raise serum T3 levels in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of myxedema coma: report on three successfully treated cases with nasogastric or intravenous administration of triiodothyronine. Pereira, VG., Haron, ES., Lima-Neto, N., et al.[2018]

In a study of 21 high-risk patients with differentiated thyroid cancer (DTC) who did not achieve target TSH levels on levothyroxine alone, the addition of liquid liothyronine (L-T3) helped all patients reach the desired TSH suppression after dose adjustments.

The use of liquid L-T3 was safe, with no adverse events reported, and allowed for individualized dosing based on body weight, making it a promising option for optimizing TSH levels in patients with DTC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liquid liothyronine to obtain target TSH in differentiated thyroid cancer patients. Trimboli, P., Centanni, M., Virili, C.[2022]

The pharmacokinetics (PK) of L-triiodothyronine (LT3) in patients without endogenous thyroid hormone production was characterized, showing a rapid distribution phase and a slow elimination phase, which is crucial for designing effective combination therapies with levothyroxine (LT4).

A proposed dosing strategy of low-dose LT3 (0.07 mcg/kg twice daily) in combination with LT4 can maintain serum T3 levels within the reference range, minimizing the risk of supraphysiologic levels and ensuring safer treatment for thyroid cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of L-Triiodothyronine in Patients Undergoing Thyroid Hormone Therapy Withdrawal. Van Tassell, B., Wohlford, GF., Linderman, JD., et al.[2020]

Poly-zinc-liothyronine (PZL) capsules provide a more stable release of T3 hormone compared to traditional liothyronine (LT3), resulting in a lower peak and a longer duration of elevated T3 levels in the blood, which is beneficial for managing hypothyroidism.

In a study with hypothyroid male Wistar rats, PZL treatment led to a more gradual decrease in serum TSH levels and restored T3-dependent biological effects, indicating its potential for improved long-term management of thyroid hormone levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metal Coordinated Poly-Zinc-Liothyronine Provides Stable Circulating Triiodothyronine Levels in Hypothyroid Rats. Da Conceição, RR., Fernandes, GW., Fonseca, TL., et al.[2020]

Combined treatment with levothyroxine and liothyronine for hypothyroidism has shown potential benefits in mood, quality of life, and psychometric performance in some studies, suggesting it may be preferred by patients over levothyroxine alone.

Despite these potential benefits, the addition of liothyronine could lead to adverse events, and until more clear advantages are established, levothyroxine alone remains the recommended treatment for hypothyroidism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of hypothyroidism with levothyroxine or a combination of levothyroxine plus L-triiodothyronine. Escobar-Morreale, HF., Botella-Carretero, JI., Morreale de Escobar, G.[2015]

In a study of nine depressed patients receiving levothyroxine (T4) for thyroid disease, seven patients showed a positive response to T3 augmentation therapy after not responding to standard antidepressant treatments.

The findings suggest that T3 may have a unique role in enhancing the effects of antidepressants in patients with thyroid disease, indicating a potential mechanism for thyroid hormone involvement in depression treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T3 augmentation of antidepressant treatment in T4-replaced thyroid patients. Cooke, RG., Joffe, RT., Levitt, AJ.[2013]

A single dose of 50-mcg liothyronine in 12 healthy participants resulted in a peak in triiodothyronine levels at 2.5 hours, followed by a transient increase in heart rate that was significant by 5 hours after administration.

The administration of liothyronine led to a sustained suppression of TSH levels for 2-3 days, indicating that while the increase in triiodothyronine was short-lived, its effects on TSH were prolonged.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-dose T3 administration: kinetics and effects on biochemical and physiological parameters. Jonklaas, J., Burman, KD., Wang, H., et al.[2021]

A 78-year-old woman developed severe hypothyroidism after total thyroidectomy for hyperthyroidism, which worsened despite increasing doses of levothyroxine, leading to respiratory failure.

The addition of liothyronine (T3) to her treatment resulted in complete recovery, indicating that her body had impaired conversion of T4 (thyroxine) to T3 (triiodothyronine), which was crucial for her recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypothyroidism and muscular respiratory failure successfully treated with liothyronine. Finsterer, J., Prainer, C., Stöllberger, C., et al.[2013]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04115514

NCT04115514 | Treatment of ARDS With Instilled T3 It is hypothesized that instillation of Liothyronine Sodium (T3) into the airspace will be safe, well tolerated, and will increase alveolar fluid clearance ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0022356524257384

A Preclinical Safety Study of Thyroid Hormone Instilled into ... This study enabled Food and Drug Administration approval of a phase I/II clinical trial of T3 instillation in patients with ARDS, including coronavirus disease ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33127750/

A Preclinical Safety Study of Thyroid Hormone Instilled into ... This preclinical safety study has paved the way for a phase I/II study to determine the safety and tolerability of a T3 formulation delivered into the lungs of ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7640752/

Liothyronine and Desiccated Thyroid Extract in the Treatment ... This dogma has been challenged by findings that, in LT4-treated hypothyroid patients with normal serum TSH, serum T3 levels are ∼10% lower whereas serum T4 ...

5. htx-research.s3.amazonaws.com htx-research.s3.amazonaws.com/Thyroxy-Preclinical.pdf

A Preclinical Safety Study of Thyroid Hormone Instilled into ... This study enabled Food and Drug Administration approval of a phase I/II clinical trial of T3 instillation in patients with. ARDS, including ...

6. experts.umn.edu experts.umn.edu/en/publications/a-preclinical-safety-study-of-thyroid-hormone-instilled-into-the-

A preclinical safety study of thyroid hormone instilled into ... This preclinical safety study has paved the way for a phase I/II study to determine the safety and tolerability of a T3 formulation delivered ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04115514?tab=history&a=10

Record History | ver. 10: 2024-10-23 | NCT04115514 This table shows all the versions of this study record arranged in order by submitted date. To view one version of the study record, click the submitted ...