Levothyroxine Dosing for Hypothyroidism in Older Adults (DOT4 Trial)
Palo Alto (17 mi)Age: 65+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: University of Pennsylvania
No Placebo Group
Prior Safety Data
Approved in 6 jurisdictions
Trial Summary
What is the purpose of this trial?Our overall goal is to determine the clinical consequences of allowing greater flexibility in LT4 dosing in older individuals who take LT4.
What safety data exists for Levothyroxine treatment?Levothyroxine Sodium is a well-established treatment for hypothyroidism, with various formulations available, including tablets, softgel capsules, and liquid forms. Safety data indicates that it is effective in maintaining thyroid hormone levels when dosed appropriately. Special care is needed in older adults and those with coronary artery disease, where lower initial doses are recommended to avoid cardiac events. Over-replacement can lead to osteoporosis, especially in postmenopausal women. Liquid formulations like Tirosint SOL are particularly beneficial for patients with malabsorption issues and are considered safe for use in various populations, including the elderly. However, caution is advised to avoid over-treatment, especially in neonates.236910
Is the drug Levothyroxine Sodium a promising treatment for hypothyroidism in older adults?Yes, Levothyroxine Sodium is a promising drug for treating hypothyroidism in older adults. It helps improve their overall health, cognitive abilities, and quality of life by replacing the missing thyroid hormone. It is the preferred choice for managing hypothyroidism and can be adjusted to meet individual needs, making it effective for older patients.1241011
What data supports the idea that Levothyroxine Dosing for Hypothyroidism in Older Adults is an effective drug?The available research shows that Levothyroxine Sodium is the preferred drug for treating hypothyroidism. It helps achieve a normal thyroid state, which is important for managing the condition. Studies indicate that different forms of Levothyroxine, like liquid and softgel capsules, can be more effective for some patients compared to tablets. For example, switching from tablet to liquid Levothyroxine has been shown to better restore normal thyroid levels in patients who had high levels while on tablets. This suggests that Levothyroxine is effective in treating hypothyroidism, especially when the right form and dosage are used.257810
Do I have to stop taking my current medications for the trial?The trial requires you to stop taking certain medications that interfere with thyroid function or tests, such as liothyronine (LT3), thyroid extracts, and Tirosint. If you're on these, you would need to stop them to participate.
Eligibility Criteria
This trial is for community-dwelling individuals aged 65 or older who have been diagnosed with hypothyroidism for at least 6 months, are on a stable dose of Levothyroxine Sodium (75-200 mcg per day), and can take oral medication. They must be able to follow the study procedures throughout its duration. People with hypopituitarism, history of thyroid cancer requiring TSH suppression, severe kidney issues (GFR <30), or those taking certain thyroid medications cannot participate.Inclusion Criteria
I have been diagnosed with hypothyroidism for at least 6 months and am on a stable dose of thyroid medication.
Exclusion Criteria
I have been diagnosed with hypopituitarism.
I have had thyroid cancer and need treatment to lower my TSH levels.
I am currently using medications that affect my thyroid function.
My kidney function is low, with a GFR under 30.
Treatment Details
The trial aims to explore the effects of more flexible dosing schedules of Levothyroxine Sodium (LT4) in older adults with hypothyroidism. It will assess how different dosing regimens might impact overall health and management of the condition.
2Treatment groups
Experimental Treatment
Active Control
Group I: Higher TSH groupExperimental Treatment1 Intervention
Target TSH level of 5.5-7.0 mU/L
Group II: Lower TSH GroupActive Control1 Intervention
Target TSH level of 0.5-2.0 mU/L
Levothyroxine Sodium is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:
🇪🇺 Approved in European Union as Levothyroxine Sodium for:
- Hypothyroidism
- Thyroid nodules
- Thyroid cancer
🇺🇸 Approved in United States as Levothyroxine Sodium for:
- Hypothyroidism
- Thyroid nodules
- Thyroid cancer
- Goiter
🇨🇦 Approved in Canada as Levothyroxine Sodium for:
- Hypothyroidism
- Thyroid nodules
- Thyroid cancer
🇯🇵 Approved in Japan as Levothyroxine Sodium for:
- Hypothyroidism
- Thyroid nodules
- Thyroid cancer
🇨🇳 Approved in China as Levothyroxine Sodium for:
- Hypothyroidism
- Thyroid nodules
- Thyroid cancer
🇨🇭 Approved in Switzerland as Levothyroxine Sodium for:
- Hypothyroidism
- Thyroid nodules
- Thyroid cancer
Find a clinic near you
Research locations nearbySelect from list below to view details:
Penn Medicine, Smilow Translational Research CenterPhiladelphia, PA
Loading ...
Who is running the clinical trial?
University of PennsylvaniaLead Sponsor
National Institute on Aging (NIA)Collaborator
References
Estimation of a physiologic replacement dose of levothyroxine in elderly patients with hypothyroidism. [2013]We gave graded doses of levothyroxine sodium to 11 elderly hypothyroid subjects (mean age, 66.1 years). The daily levothyroxine sodium dose was initially 75 micrograms or less, and was increased by 25 micrograms every six weeks. Serum total thyroxine, total triiodothyronine, and basal thyrotropin levels were measured at the start of the study and at the end of each six-week dose period. A protirelin (thyrotropin-releasing hormone) test was performed when the thyrotropin level returned to normal. Mean daily levothyroxine sodium doses that normalized serum thyrotropin levels and protirelin test were 110 +/- 8 micrograms and 113 +/- 9 micrograms, respectively. Serial basal thyrotropin determinations during stepwise increments in levothyroxine dose indicated physiologic hormone replacement. As determined in our elderly patients, levothyroxine replacement dose was a third less than that formerly recommended.
[Treatment of hypothyroidism]. [2013]Levothyroxine sodium (LT4) is the treatment of choice for the management of hypothyroidism. The aim of the treatment is to obtain a permanent clinical and biological (normal TSH values) euthyroid state. Before initiating therapy, hypothyroidism has to be confirmed and, in adults, the risk of coronary heart disease to be evaluated. Adults require approximately 1.6-1.7 micrograms/kg/day for full replacement. Replacement doses may vary with various factors (age, weight, pregnancy, cause of the thyroid disease, degree of failure). Therapy is initiated gradually, usually starting with 50-100 micrograms LT4 in the adults without coronary heart disease risk. For older patients or patients at risk for cardiac disease, a lower initial dosage (12.5-25 micrograms LT4) and lower increments are indicated. Once the appropriate dose has been established, periodic monitoring, first at six months and then annually or every 6 months, is essential. Patients should not be evaluated before 6 weeks with the same dosage. Patient information is also important to improve compliance. Therapy for subclinical hypothyroidism is controversial. It is probably advisable if thyroid autoantibodies are positive and particularly if non specific signs or symptoms are present. Other forms (central hypothyroidism, iatrogenic transient and congenital forms, supra substitutive therapy for thyroid cancers) require a specific and specialised approach.
Optimizing treatment of hypothyroidism. [2019]Several thyroid hormone preparations are currently available, including levothyroxine sodium (thyroxine), liothyronine (triiodothyronine), and desiccated thyroid extract, as well as a combination of levothyroxine sodium and liothyronine. Levothyroxine sodium monotherapy at an appropriate daily dose provides uniform levels of both thyroxine and triiodothyronine in the circulation without diurnal variation. Therefore, it is the preparation of choice in most patients with hypothyroidism of both the primary and central types. A normal thyrotropin (TSH) level of 1-2 mU/L is considered the determinant of optimal daily levothyroxine sodium dose in patients with primary hypothyroidism, whereas normal thyroxine and triiodothyronine levels in the mid or upper normal range may denote optimal replacement in patients with central hypothyroidism. Optimal daily levothyroxine sodium dose may be determined according to serum TSH level at the time of diagnosis of primary hypothyroidism. Initial administration of close to the full calculated dose of levothyroxine sodium is appropriate for younger patients, reducing the need for follow-up visits and repeated laboratory testing for dose titration. In the elderly and in patients with a history of coronary artery disease (CAD), the well established approach of starting with a low dose and gradually titrating to the full calculated dose is always the best option. Levothyroxine sodium can and should be continued in patients receiving treatment for CAD. Even minor over-replacement during initial titration of levothyroxine sodium should be avoided, because of the risk of cardiac events. Chronic over-replacement may induce osteoporosis, particularly in postmenopausal women, and should also be avoided.
Hypothyroidism: challenges when treating older adults. [2013]Hypothyroidism frequently affects older adults' general sense of health, their cognitive abilities, and quality of life. Management decisions regarding when to start treatment and at what dosage to begin medication are influenced by both laboratory values and patient symptoms. Although specific guidelines regarding management of hypothyroidism in older adults do not exist, general recommendations include initiating hormone replacement with levothyroxine (Levoxyl(®), Synthroid(®), and others) at 12.5 mcg to 25 mcg and titrating the dose slowly based on response at 6-week intervals. Multiple medications and certain foods can interact with levothyroxine; therefore, the best dosage time is when a person is fasting or 4 hours postprandial. Using a consistent brand-name drug for hormone replacement with levothyroxine is important due to variations in the active ingredient in generic formulations. Providers need to be aware of the prevalence of hypothyroidism and management issues when caring for older adults.
Comparison of TSH Levels with Liquid Formulation Versus Tablet Formulations of Levothyroxine in the Treatment of Adult Hypothyroidism. [2022]A great number of factors can interfere with levothyroxine (LT4) tablet absorption, leading to increased serum thyroid-stimulating hormone (TSH) levels and, accordingly, to increased LT4 requirements. LT4 oral solution (LT4-OS) is a novel formulation with a pharmacokinetics profile different from those of tablets. The aim of this study was to retrospectively evaluate whether serum TSH levels were decreased after switching adult hypothyroid patients from the tablet to LT-OS.
New levothyroxine formulation meeting 95-105% specification over the whole shelf-life: results from two pharmacokinetic trials. [2018]Small levothyroxine (L-T4) dose changes can lead to significant clinical effects. To ensure thyroid hormone levels are safely maintained, authorities are increasingly adopting stricter potency specifications for L-T4, the most stringent of these being 95-105% of the labeled dose over the whole shelf-life. Levothyroxine sodium (Euthyrox, Eutirox, Lévothyrox ) has been reformulated, and two studies performed, to ensure bioequivalence to the currently marketed formulation and dosage form proportionality of the new formulation.
IN PATIENTS WITH SUBCLINICAL HYPOTHYROIDISM WHILE IN THERAPY WITH TABLET L-T4, THE LIQUID L-T4 FORMULATION IS MORE EFFECTIVE IN RESTORING EUTHYROIDISM. [2022]Levothyroxine (L-T4) is the standard therapy of hypothyroidism. Our purpose was to compare the effectiveness of the L-T4 liquid formulation with respect to L-T4 tablet in hypothyroid patients without malabsorption or drug interference. Twenty-one subjects with high thyroid-stimulating hormone (TSH) values under therapy with L-T4 tablets were switched to liquid L-T4 at the same dosage given 30 minutes before breakfast.
Thyroxine Treatment With Softgel Capsule Formulation: Usefulness in Hypothyroid Patients Without Malabsorption. [2022]Levothyroxine sodium (LT4) is the therapy of choice for hypothyroidism. In the last decade, new LT4 formulations, such as liquid and softgel capsules, became available. Even if some evidence has been reached in the efficacy of liquid LT4 in patients with suboptimal TSH on tablet LT4, the usefulness of softgel LT4 has been rarely studied. This study aimed at evaluating the effect of switching from tablet to softgel LT4 patients without increased need for LT4. TSH was used as proxy of LT4 bioavailability and effectiveness.
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]Hypothyroidism is a common endocrine disorder affecting 3-15% of the adult population in subclinical form and 0.3-0.8% as overt disease. The mainstay of treatment is replacement monotherapy with levothyroxine (LT4). Currently several oral LT4 formulations including tablets, softgel capsules, and liquid formulations are available. Liquid LT4 is manufactured as LT4 solution in 85% glycerol and 96% ethanol and as LT4 solution in purified water and glycerol. The latest formulation, Tirosint SOL, gained FDA approval in 2017. To evaluate the clinical utility of liquid LT4 we reviewed the literature using three databases: PubMed/MEDLINE, Scopus, and Embase and found 405 articles among which 23 prospective and two retrospective studies were further evaluated. Finally, several case reports on rare clinical conditions were discussed. Our review demonstrated that liquid LT4 was more effective than tablet formulation in patients with malabsorption caused by interfering diseases, drugs, and bariatric surgery. The better pharmacokinetics of liquid LT4 was also confirmed in subjects without malabsorption: patients on replacement or suppressive therapy, who switched from tablet to liquid formulation in equivalent dose, gained better hormonal control, and required less frequent TSH measurements. The drug also appeared effective and easy to handle in patients fed by enteric tube. Liquid LT4 appeared equally effective whenever taken before or during breakfast. The analysis of the drug utility in particular populations including newborns, pregnant women, and the elderly confirmed the high value and safety of liquid LT4. However, in neonates the higher incidence of TSH suppression on liquid in comparison to tablet LT4 therapy was noted, and particular attention to avoid over-treatment must be paid. Concluding: the literature review revealed that liquid LT4 is especially advantageous in patients with malabsorption and the critically ill, but it seems also very promising in common therapy. The lack of alcohol content in the new formulation makes Tirosint SOL especially attractive.
Levothyroxine Sodium - Thyroid Hormone Replacement Therapy for Hypothyroidism: A Review of Patent Literature. [2023]Levothyroxine Sodium is a thyroid hormone replacement therapy for Hypothyroidism. Levothyroxine Sodium is approved to treat Hypothyroidisim, to suppress thyroid hormone release from cancerous thyroid nodules, and to prevent the growth of goiters. In addition, it is also used to treat conditions such as myxedema, cretinism, and obesity.
Levothyroxine liquid oral substitution as an alternative treatment for refractory hypothyroidism due to gastrointestinal malabsorption: A case report. [2023]Tablets of levothyroxine (LT4) are the most used form for the treatment of hypothyroidism. Some patients may present with refractory hypothyroidism despite a high daily LT4 dose. We report the case of a 49-year-old woman who was admitted to our department for refractory hypothyroidism. She was treated with 300 μg oral LT4 tablets daily (3.9 μg/kg/day). Despite good compliance and regular intake of high doses of LT4, she had persistent symptoms of hypothyroidism and a thyroid-stimulating hormone level of 92.4 mIU/L. LT4 absorption test was consistent with the diagnosis of malabsorption. Etiological investigations revealed Helicobacter pylori gastritis. Helicobacter infection was adequately treated, but symptoms of hypothyroidism and elevated thyroid-stimulating hormone persisted. Increased LT4 doses (400 μg) failed to normalize thyroid-stimulating hormone levels. Thus, she was put on LT4 liquid form at a dose of 80 drops/day per day (400 µg). Two weeks later, she presented with clinical and biological improvement with a normal free thyroxine level of 1.14 ng/dL. Patients with gastrointestinal disorders may present with refractory hypothyroidism despite increasing doses of LT4. Switching to liquid formulation may resolve this problem.