Deprescribing Thyroid Hormone for Hypothyroidism

Recruiting at 2 trial locations

Overseen By Brittany Gay

Age: 65+

Sex: Any

Trial Phase: Academic

Sponsor: University of Michigan

Must be taking: Thyroid hormones

Disqualifiers: Thyroid cancer, Secondary hypothyroidism, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

900 Participants Needed

Trial Summary

What is the purpose of this trial?

The proposed study focuses on testing a novel adapted evidence-based multilevel intervention, Deprescribing Thyroid Hormone In Older Adults (D-THIO), to support thyroid hormone deprescribing (dose de-escalation and/or discontinuation) in older adults with thyroid hormone overtreatment and/or misuse and reduce patient harm. Findings from this study will lay the groundwork for broad implementation of D-THIO and serve as a model for deprescribing inappropriate medications for other endocrine conditions and conditions with biochemical monitoring.

Will I have to stop taking my current medications?

The trial focuses on reducing or stopping thyroid hormone treatment in older adults. If you are taking thyroid hormone, you may need to adjust or stop it as part of the study.

What data supports the effectiveness of the drug Levothyroxine for deprescribing thyroid hormone in older adults?

Research shows that Levothyroxine is commonly used to treat hypothyroidism, and some patients can successfully stop taking it while maintaining normal thyroid function. Up to a third of patients remained stable after discontinuing the drug, especially those with milder forms of hypothyroidism. ^{1 2 3 4 5}

Is it safe to deprescribe thyroid hormone in humans?

Levothyroxine (LT4) is generally considered safe when used to treat hypothyroidism, but safety can vary based on factors like age, weight, and heart health. It's important to start with a lower dose in older adults or those at risk for heart disease and to monitor regularly. ^{1 3 5 6 7}

How is the drug D-THIO different from other treatments for hypothyroidism?

D-THIO focuses on deprescribing, or reducing the use of, thyroid hormone replacement therapy like Levothyroxine (LT4) in older adults, which is unique because it aims to identify patients who may not need lifelong hormone therapy and can maintain normal thyroid function without it. ^{1 2 3 4 6}

Research Team

Maria Papaleontiou

Principal Investigator

University of Michigan

Eligibility Criteria

This trial is for older adults who are being overtreated with thyroid hormone or using it inappropriately. The goal is to safely reduce or stop their medication to prevent harm.

Inclusion Criteria

Primary care physicians, endocrinologists, geriatricians, and Advanced Practice Providers (APPs) who practice at University of Michigan, Henry Ford Health System or University of California San Francisco (UCSF) and prescribe thyroid hormone for eligible patients identified above are eligible for study participation.

Patients without cognitive impairment

English speaking

Exclusion Criteria

I have been diagnosed with thyroid cancer.

My doctor does not prescribe thyroid hormone treatments.

I have a condition where my thyroid doesn't produce enough hormones due to a pituitary issue.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the D-THIO intervention or enhanced usual care for thyroid hormone deprescribing

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• D-THIO (Deprescribing Thyroid Hormone In Older Adults)

Trial Overview The study tests D-THIO, a strategy to help doctors and patients lower or stop unnecessary thyroid hormone use, compared with the usual care practices.

Participant Groups

Group I: D-THIO (Deprescribing Thyroid Hormone In Older Adults) Experimental Treatment 1 Intervention

D-THIO is an innovative adapted multilevel intervention. Providers in the intervention arm will receive: 1) an introductory letter, and 2) the D-THIO pharmaceutical opinion via EMR-compatible correspondence. After randomization of their treating providers, patients in the intervention arm will receive a study packet including: 1) introductory letter, and 2) the D-THIO patient brochure (educational EMPOWER brochure).

Group II: Enhanced usual care Active Control 1 Intervention

This arm will receive enhanced usual care. Providers in the control arm will receive: 1) an introductory letter signed by the PI and site-PIs, and 2) the ATA hypothyroidism pocket card via EMR. Patients in the control arm will receive a study packet including: 1) introductory letter, and 2) the ATA patient brochure.

D-THIO (Deprescribing Thyroid Hormone In Older Adults) is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Levothyroxine for:

• Hypothyroidism
• Subclinical Hypothyroidism

Approved in European Union as Levothyroxine for:

• Hypothyroidism
• Subclinical Hypothyroidism

Approved in Canada as Levothyroxine for:

• Hypothyroidism
• Subclinical Hypothyroidism

Who Is Running the Clinical Trial?

University of Michigan

Lead Sponsor

Trials

1,891

Recruited

6,458,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

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]

In a study of 5437 participants treated with different thyroid hormone therapies, those using desiccated thyroid extract (DTE) or a combination of levothyroxine and liothyronine (LT4 + LT3) had lower outpatient care utilization for cardiovascular disease and bone health compared to those on levothyroxine (LT4) alone (3.5% vs 7.7%).

After adjusting for various factors, there were no significant differences in emergency or hospital care utilization between the treatment groups, suggesting that DTE and LT4 + LT3 may not lead to increased health care needs compared to LT4 monotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A cross-sectional analysis of cardiovascular and bone healthcare utilization during treatment with thyroid hormone. Penna, GC., Bianco, AC., Ettleson, MD.[2023]

Obese females require a higher total dose of levothyroxine (LT4) to achieve a normal thyroid-stimulating hormone (TSH) level compared to nonobese females, with mean doses of 146 μg vs. 102 μg, respectively, although the dose per kilogram of body weight is similar.

The study suggests that the standard LT4 dosing approach may not be accurate for obese patients, indicating a need for lower initial doses in this group to avoid variability in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LEVOTHYROXINE REPLACEMENT IN OBESE HYPOTHYROID FEMALES AFTER TOTAL THYROIDECTOMY. Glymph, K., Gosmanov, AR.[2022]

About one-third of patients (37.2%) who discontinued levothyroxine (LT4) therapy remained euthyroid, indicating that some patients can successfully manage without this medication after careful evaluation.

Patients with a prior diagnosis of subclinical hypothyroidism were more likely to remain euthyroid after discontinuation compared to those with overt hypothyroidism, suggesting that initial diagnosis may influence the success of stopping LT4 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Outcomes After Discontinuation of Thyroid Hormone Replacement: A Systematic Review and Meta-Analysis. Burgos, N., Toloza, FJK., Singh Ospina, NM., et al.[2022]

Levothyroxine sodium (LT4) is the primary treatment for hypothyroidism, aiming to achieve normal thyroid-stimulating hormone (TSH) levels, with dosages typically starting at 50-100 micrograms for adults without heart disease risk, and lower for older patients or those at risk.

Regular monitoring of TSH levels is crucial after establishing the appropriate LT4 dose, with evaluations starting at six months and continuing annually, to ensure effective management of the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of hypothyroidism]. Massol, J.[2013]

In a study of over 10,000 patients treated with levothyroxine (LT4), the use of statins increased significantly after starting LT4 therapy, indicating a potential link between thyroid hormone normalization and lipid management.

Patients on LT4 had higher rates of statin prescriptions compared to those not on LT4, with odds ratios indicating a strong association, suggesting that LT4 treatment may influence lipid metabolism and necessitate further investigation into this relationship.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Statins Among Patients Taking Levothyroxine: an Observational Drug Utilization Study Across Sites. Idrees, T., Prieto, WH., Casula, S., et al.[2022]

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]

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

A cross-sectional analysis of cardiovascular and bone healthcare utilization during treatment with thyroid hormone. [2023]

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

LEVOTHYROXINE REPLACEMENT IN OBESE HYPOTHYROID FEMALES AFTER TOTAL THYROIDECTOMY. [2022]

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

Clinical Outcomes After Discontinuation of Thyroid Hormone Replacement: A Systematic Review and Meta-Analysis. [2022]

5. France pubmed.ncbi.nlm.nih.gov

[Treatment of hypothyroidism]. [2013]

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

Use of Statins Among Patients Taking Levothyroxine: an Observational Drug Utilization Study Across Sites. [2022]

7. 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]