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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to help older adults safely reduce or stop thyroid hormone treatment if overused or misused. Researchers are testing a new approach called D-THIO (Deprescribing Thyroid Hormone In Older Adults), which educates and guides both patients and healthcare providers. The goal is to minimize potential harm from unnecessary thyroid medication. This trial suits those aged 65 and older who take thyroid hormone medication and have low thyroid-stimulating hormone levels, a measure of thyroid activity. As an unphased trial, it offers participants the chance to contribute to research that could enhance medication safety for older adults.

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 prior data suggests that the D-THIO intervention is safe for older adults?

Research has shown that reducing or stopping thyroid hormone treatment in older adults, as demonstrated in the D-THIO study, is generally safe and well-tolerated. Studies have found that patients who may no longer need thyroid hormone often achieve good results without serious side effects when they reduce or stop their medication. Most patients maintain stable thyroid levels after adjusting their medication. While some may experience mild symptoms, these are usually easy to manage. The goal is to ensure patients take only the medication they truly need, helping to avoid unnecessary use and potential harm. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the D-THIO approach because it offers a new perspective on managing hypothyroidism, especially in older adults. Unlike the standard treatment, which typically involves lifelong hormone replacement with levothyroxine, D-THIO focuses on safely reducing or stopping thyroid hormone therapy when it might no longer be necessary. This method emphasizes personalized care by educating both healthcare providers and patients, potentially reducing unnecessary medication use and enhancing quality of life. By providing tailored information and facilitating informed discussions, D-THIO aims to address over-treatment and optimize health outcomes for older adults.

What evidence suggests that the D-THIO intervention is effective for deprescribing thyroid hormone in older adults?

Research shows that many older adults take more thyroid hormone than needed, leading to health problems. In this trial, participants in one arm will receive the D-THIO approach, which helps safely reduce or stop unnecessary thyroid hormone use. Studies have found that properly cutting back on medication can improve health. The D-THIO method provides support and education to help doctors and patients make informed decisions about thyroid hormone use. Early results suggest this strategy effectively reduces overtreatment and encourages better health choices. ^{2 3 4 6 7}

Who Is on the Research Team?

Maria Papaleontiou

Principal Investigator

University of Michigan

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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 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]

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]

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]

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