Hormone Replacement Therapy for Hypothyroidism

Recruiting at 37 trial locations

Overseen By Sention Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sention Therapeutics, LLC

Must be taking: Levothyroxine

Disqualifiers: Pregnancy, Breastfeeding, Other clinical study, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

490 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new hormone replacement therapy called ST-1891 in patients with primary hypothyroidism. The goal is to help patients whose thyroid glands don't produce enough hormones. Levothyroxine has been the standard treatment for hypothyroidism since the 1950s.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must have been on a stable dose of levothyroxine for at least 3 months before joining. You cannot start or change other medications during the trial.

What data supports the effectiveness of the drug Levothyroxine for treating hypothyroidism?

Levothyroxine is widely used to replace thyroid hormones in people with hypothyroidism, as it effectively corrects hormone deficiency, according to multiple studies. It is considered the treatment of choice for this condition, helping patients achieve normal thyroid hormone levels. ^{1 2 3 4 5}

Is hormone replacement therapy with levothyroxine generally safe for humans?

Levothyroxine, used for treating hypothyroidism, is generally considered safe for humans. It is available in various forms, including tablets and liquid, and is effective in maintaining thyroid hormone levels. However, care must be taken to avoid over-treatment, especially in newborns, as it can lead to suppressed thyroid-stimulating hormone (TSH) levels. ^{2 4 6 7 8}

How is the drug Levothyroxine unique for treating hypothyroidism?

Levothyroxine is a standard treatment for hypothyroidism, but it is unique because it is often used alone or in combination with T3 to tailor therapy to individual needs, potentially improving quality of life and cognitive function. It is also versatile, being used for other conditions like thyroid cancer and goiter prevention. ^{5 7 9 10 11}

Eligibility Criteria

Inclusion Criteria

On a stable daily dose of levothyroxine for the 3 months prior to Screening

Willing to give written informed consent for the Study

You have been taking levothyroxine for your thyroid for at least a year before the screening.

Exclusion Criteria

Anticipated initiation or change in concomitant medications

Currently participating in another clinical study or have received active treatment with an investigational drug within 30 days or 5 half-lives of the investigational drug of Screening, whichever is longer

You have a medical condition or had surgery that might affect how your body processes ST-1891 or levothyroxine.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive hormone replacement therapy with ST-1891 or levothyroxine

8-12 weeks

Crossover

Participants switch from one treatment to the other to evaluate comparative efficacy

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Levothyroxine
• ST-1891

Participant Groups

Group I: ST-1891 Experimental Treatment 1 Intervention

Group II: Levothyroxine Active Control 1 Intervention

Levothyroxine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Levothyroxine for:

• Hypothyroidism
• Thyroid cancer
• Euthyroid goiters

Approved in European Union as Levothyroxine for:

• Hypothyroidism
• Thyroid cancer
• Euthyroid goiters

Approved in Canada as Levothyroxine for:

• Hypothyroidism
• Thyroid cancer
• Euthyroid goiters

Who Is Running the Clinical Trial?

Sention Therapeutics, LLC

Lead Sponsor

Trials

1

Recruited

490+

Findings from Research

Levothyroxine (LT4) is the preferred treatment for hypothyroidism among Irish endocrinologists, with 81.3% of surveyed doctors supporting its use, although some also consider combination therapies like liothyronine for certain patients.

A notable 51% of endocrinologists might prescribe thyroid hormones to euthyroid patients under specific conditions, such as for women with thyroid auto-antibodies seeking pregnancy, indicating a nuanced approach to treatment despite existing guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Thyroid Hormones in Hypothyroid and Euthyroid Patients: A THESIS questionnaire survey of members of the Irish Endocrine Society. Mustafa, M., Ali, E., McGowan, A., et al.[2023]

L-Thyroxin Henning 100 demonstrated significantly higher bioavailability compared to Eferox 100, leading to higher free thyroxine (fT4) levels and a greater reduction in serum TSH levels after 14 days of treatment in a study involving 60 euthyroid volunteers.

The study suggests that when switching between different LT4 preparations, regular monitoring of serum TSH and fT4 levels is essential to prevent metabolic imbalances, as individual factors like gender and body weight can influence bioavailability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Randomized, double-blind crossover study of bioavailability of levothyroxine]. Krehan, A., Dittmar, M., Hoppen, A., et al.[2019]

In a study of 32 adults with primary hypothyroidism, the fixed combination therapy of levothyroxine/liothyronine (LT4/LT3) resulted in significantly lower free T4 levels compared to standard LT4 treatment, but did not affect TSH or T3 levels.

Despite some patients on LT4/LT3 experiencing elevated T3 levels and an increased heart rate, the combination therapy did not show clear clinical benefits in terms of lipid profile, body weight, or quality of life, suggesting that further research is needed to explore its efficacy in specific populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of hypothyroidism with levothyroxine plus liothyronine: a randomized, double-blind, crossover study. Kaminski, J., Miasaki, FY., Paz-Filho, G., et al.[2023]

In a study of 36 young adult patients, those with congenital hypothyroidism (CH) required a significantly higher daily dosage of levothyroxine (l-T4) to achieve normal thyroid hormone levels compared to those who had hypothyroidism after total thyroidectomy (1.73 vs 2.16 μg/kg).

Despite achieving normal thyroid hormone levels, patients with CH had higher serum TSH levels than those with surgical hypothyroidism, suggesting that their hypothalamus-pituitary-thyroid axis may be set differently due to a lack of thyroid hormones since fetal life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The different requirement of L-T4 therapy in congenital athyreosis compared with adult-acquired hypothyroidism suggests a persisting thyroid hormone resistance at the hypothalamic-pituitary level. Bagattini, B., Cosmo, CD., Montanelli, L., et al.[2016]

The new formulation of levothyroxine (L-T4) has been shown to be bioequivalent to the current formulation, with a geometric mean ratio of 99.3% for the area under the curve (AUC) and 101.7% for maximum concentration (Cmax), ensuring consistent therapeutic effects.

This reformulated L-T4 meets strict potency specifications and demonstrates dosage form proportionality, allowing for more precise dosing tailored to individual patient needs, which enhances safety in thyroid hormone management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New levothyroxine formulation meeting 95-105% specification over the whole shelf-life: results from two pharmacokinetic trials. Gottwald-Hostalek, U., Uhl, W., Wolna, P., et al.[2018]

In a study of 59 euthyroid children with Hashimoto thyroiditis, treatment with levothyroxine (L-T4) significantly reduced thyroid volume over 36 months, with a notable decrease in the treatment group compared to the observation group.

Despite the reduction in thyroid volume, L-T4 treatment did not affect thyroid function or serum thyroid antibodies, indicating that while it may help manage thyroid size, it does not alter the underlying autoimmune condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Levothyroxine Treatment of Euthyroid Children with Autoimmune Hashimoto Thyroiditis: Results of a Multicenter, Randomized, Controlled Trial. Dörr, HG., Bettendorf, M., Binder, G., et al.[2022]

Liquid levothyroxine (LT4) formulations, particularly Tirosint SOL, are more effective than tablet forms for patients with malabsorption issues, leading to better hormonal control and less frequent TSH measurements.

The liquid LT4 is safe and effective for various populations, including newborns and pregnant women, but caution is needed in neonates due to a higher risk of TSH suppression compared to tablet LT4.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expert opinion on liquid L-thyroxine usage in hypothyroid patients and new liquid thyroxine formulation - Tirosint SOL [Opinia ekspertów dotycząca stosowania płynnej postaci lewotyroksyny oraz nowego preparatu Tirosint SOL u chorych na niedoczynność tarczycy]. Gietka-Czernel, M., Hubalewska-Dydejczyk, A., Kos-Kudła, B., et al.[2021]

Current evidence suggests that combining T(3) and T(4) treatment may improve quality of life and cognitive function in hypothyroid patients, indicating a potential shift from traditional levothyroxine therapy alone.

The review highlights the need for personalized thyroid hormone replacement regimens and calls for further randomized controlled studies to explore the benefits and optimal ratios of T(4) and T(3) in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination treatment with T4 and T3: toward personalized replacement therapy in hypothyroidism? Biondi, B., Wartofsky, L.[2022]

Levothyroxine Sodium is an important thyroid hormone replacement therapy for hypothyroidism and has various applications, including treating goiters and certain thyroid cancers, highlighting its efficacy in managing thyroid-related conditions.

Recent patents have focused on improving the stability and formulation of Levothyroxine Sodium due to challenges like photosensitivity and oxidation, which could lead to better and more cost-effective treatments in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Levothyroxine Sodium - Thyroid Hormone Replacement Therapy for Hypothyroidism: A Review of Patent Literature. Upadhyay, U., Vora, PA., Patel, R., et al.[2023]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Use of Thyroid Hormones in Hypothyroid and Euthyroid Patients: A THESIS questionnaire survey of members of the Irish Endocrine Society. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

[Randomized, double-blind crossover study of bioavailability of levothyroxine]. [2019]

3. Brazil pubmed.ncbi.nlm.nih.gov

Treatment of hypothyroidism with levothyroxine plus liothyronine: a randomized, double-blind, crossover study. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Identifying Predictors of Prolonged Levothyroxine Dose Adjustment After Thyroidectomy. [2020]

5. England pubmed.ncbi.nlm.nih.gov

The different requirement of L-T4 therapy in congenital athyreosis compared with adult-acquired hypothyroidism suggests a persisting thyroid hormone resistance at the hypothalamic-pituitary level. [2016]

6. England pubmed.ncbi.nlm.nih.gov

New levothyroxine formulation meeting 95-105% specification over the whole shelf-life: results from two pharmacokinetic trials. [2018]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Levothyroxine Treatment of Euthyroid Children with Autoimmune Hashimoto Thyroiditis: Results of a Multicenter, Randomized, Controlled Trial. [2022]

8. Poland pubmed.ncbi.nlm.nih.gov

Expert opinion on liquid L-thyroxine usage in hypothyroid patients and new liquid thyroxine formulation - Tirosint SOL [Opinia ekspertów dotycząca stosowania płynnej postaci lewotyroksyny oraz nowego preparatu Tirosint SOL u chorych na niedoczynność tarczycy]. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Real Practice Assessment of Persistent Symptoms After Initiation of Levothyroxine. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Combination treatment with T4 and T3: toward personalized replacement therapy in hypothyroidism? [2022]

11. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Levothyroxine Sodium - Thyroid Hormone Replacement Therapy for Hypothyroidism: A Review of Patent Literature. [2023]