Thyroid Hormone Supplementation for Hypothyroidism in Hemodialysis Patients (THYROID-HD Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: University of California, Irvine
Approved in 6 jurisdictions
Trial Summary
What is the purpose of this trial?This trial tests if levothyroxine, a thyroid hormone replacement, can improve quality of life and heart health in dialysis patients with slightly high TSH levels. The medication aims to balance their thyroid hormone levels. Levothyroxine is a commonly used thyroid hormone replacement therapy that has been shown to improve heart function and physical activity without significant side effects.
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 cannot participate if you are actively taking thyroid hormone supplements or anti-thyroid medications.
What data supports the effectiveness of the drug Levothyroxine Sodium for hypothyroidism in hemodialysis patients?
Research shows that Levothyroxine Sodium can help manage hypothyroidism in patients with kidney issues, as it has been effective in preventing worsening kidney function and improving nutritional status in patients with chronic kidney disease.
12345Is levothyroxine generally safe for humans?
Levothyroxine is generally safe for humans, but there are rare cases of liver injury, especially if the dose is increased too quickly. It's important to start with a low dose and increase gradually, especially in older adults or those with heart disease, to avoid potential side effects like heart problems or bone loss.
16789How is the drug Levothyroxine Sodium unique for treating hypothyroidism in hemodialysis patients?
Levothyroxine Sodium is unique because it can be administered intravenously during hemodialysis sessions, which is beneficial for patients who cannot take oral medications. This method ensures that patients with severe hypothyroidism and non-adherence to oral treatments receive the necessary thyroid hormone replacement.
1351011Eligibility Criteria
This trial is for people aged 18-75 on hemodialysis with mild to moderate hypothyroidism, not currently treated for thyroid issues. They must have stable heart function and no severe bone disease, weigh less than 450 lbs., and not be pregnant or planning pregnancy.Inclusion Criteria
I am between 18 and 75 years old.
Exclusion Criteria
I am currently taking medication for my thyroid condition.
I am currently on dialysis.
I am currently experiencing worsening heart failure symptoms.
I have an active cancer or a history of thyroid cancer.
I have been diagnosed with osteoporosis.
I have heart issues like blocked arteries or irregular heartbeat.
I have been diagnosed with hyperthyroidism or am on medication for it.
I have had a kidney transplant.
Participant Groups
The study tests if Levothyroxine improves life quality and cardiovascular health in dialysis patients compared to a placebo. It also looks at metabolic effects like changes in body fat and energy use.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: LevothyroxineExperimental Treatment1 Intervention
Patients will be randomized to levothyroxine or placebo (similar in size, shape, and color to levothyroxine) via permuted blocks stratified by two TSH levels (\>3.0-5.0 and 5.0-10.0mIU/L) to ensure treatment balance across TSH levels. The study medications will be prepared in pill form. In the treatment arm, initial L-T4 doses will be 25mcg vs. 50mcg among patients whose TSH is \>3.0-5.0mIU/L vs. 5.0-10.0mIU/L, respectively. Patients in the placebo arm will receive an equivalent number of placebo pills daily depending upon TSH level.
The intervention period is 24 weeks. Patients will undergo up to two subsequent dose titrations after 8- and 16-weeks of treatment, based on interim TSH measurements at these time points. Patients whose TSH levels are higher or lower than the therapeutic TSH target of 0.5-3.0mIU/L will undergo a dose adjustment (+/- 25mcg), while those whose TSH levels are in target range will continue the prior dose.
Group II: PlaceboPlacebo Group1 Intervention
Patients will be randomized to levothyroxine or placebo (similar in size, shape, and color to levothyroxine) via permuted blocks stratified by two TSH levels (\>3.0-5.0 and 5.0-10.0mIU/L) to ensure treatment balance across TSH levels. The study medications will be prepared in pill form. In the treatment arm, initial L-T4 doses will be 25mcg vs. 50mcg among patients whose TSH is \>3.0-5.0mIU/L vs. 5.0-10.0mIU/L, respectively. Patients in the placebo arm will receive an equivalent number of placebo pills daily depending upon TSH level.
The intervention period is 24 weeks. Patients in the placebo arm will undergo an equivalent titration in placebo pills (as that of the experimental arm) after 8- and 16-weeks of treatment, based on interim TSH measurements at these time points.
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:
University of California IrvineOrange, CA
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Who is running the clinical trial?
University of California, IrvineLead Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Collaborator
References
Prevention of progressive renal failure by levothyroxine sodium in a diabetic patient with renal insufficiency and hypothyroidism. [2019]The progressive renal failure of a 49-year-old female diabetic patient with renal insufficiency and hypothyroidism was successfully prevented by levothyroxine sodium treatment. Her renal function worsened in parallel with the exacerbation of hypothyroidism. Cessation of progressive renal failure was observed after administration of levothyroxine sodium (0.05 mg daily) for more than 24 months. Mean slopes of reciprocal serum creatinine levels for 12 months before and after the administration of levothyroxine sodium were -1.67 x 10(-3) and +8.68 x 10(-4), respectively. It was suggested that levothyroxine sodium was effective in the prevention of progressive renal failure in this patient.
FAVORABLE EFFECT OF LEVOTHYROXINE ON NUTRITIONAL STATUS OF PATIENTS WITH STAGE 3-4 CHRONIC KIDNEY DISEASE. [2023]The aim of this study was to analyze the incidence of malnutrition in patients with stage 3-4 chronic kidney disease (CKD) and primary subclinical hypothyroidism and the effect of levothyroxine for improving nutritional status and delaying kidney disease.
[Randomized, double-blind crossover study of bioavailability of levothyroxine]. [2019]The synthetic thyroid hormone levothyroxine-sodium (LT4) is still the treatment of choice to replace thyroid hormone deficiency in hypothyroidism, and for adjuvant treatment of euthyroid goiter. A change of LT4 preparations during treatment may lead to major changes of thyroid hormone levels. In this study, we compared the bioavailability of two LT4 preparations, L-Thyroxin Henning 100 and Eferox 100.
Can levothyroxine treatment reduce urinary albumin excretion rate in patients with early type 2 diabetic nephropathy and subclinical hypothyroidism? A randomized double-blind and placebo-controlled study. [2018]To investigate the effect of levothyroxine (LT4) therapy on urinary albumin excretion rate (UAER) in early type 2 diabetic nephropathy (DN) and subclinical hypothyroidism (SCH) patients with mildly increased thyroid stimulating hormone (TSH) levels and serum thyroid peroxidase antibody (TPO-Ab) positivity.
INTRAVENOUS LEVOTHYROXINE DURING HEMODIALYSIS IN A PATIENT WITH HYPOTHYROIDISM AND NON-ADHERENCE TO ORAL MEDICATIONS. [2022]We describe an unusual and challenging clinical scenario: a patient with end-stage renal disease on hemodialysis with severely uncontrolled hypothyroidism and worsening psychosis, who refused both oral and intramuscular levothyroxine, but was successfully treated with intravenous (IV) levothyroxine given on hemodialysis days.
Drug interactions in users of tablet vs. oral liquid levothyroxine formulations: a real-world evidence study in primary care. [2019]Several medications may interact with levothyroxine (LT4) intestinal absorption or metabolism, thus reducing its bioavailability. We investigated the variability of thyroid stimulating hormone (TSH) levels and prescribed daily dosages (PDDs) of LT4 before and during potential drug-drug interactions (DDIs) in users of tablets vs. oral liquid LT4 formulations.
[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.
Liver dysfunction induced by Levothyroxine Sodium Tablets (Euthyrox®) in a hypothyroid patient with Hashimoto's thyroiditis: case report and literature review. [2020]A 49-year-old woman with hypothyroidism developed liver dysfunction after increasing dose of levothyroxine (L-T4) (Euthyrox®) from 25 μg to 50 μg. Viral hepatitis, autoimmune hepatitis and non-alcoholic steatohepatitis (NASH) were ruled out with examinations. She had no concurrent medication and had no history of infectious, chronic or any other autoimmune diseases. After cessation of Levothyroxine Sodium Tablets (Euthyrox®), liver enzymes gradually returned to normal. She was diagnosed levothyroxine-induced liver injury, based on criteria proposed in "Diagnosis and treatment guideline on drug-induced liver injury" issued by the Chinese Medical Association (2015). As an alternative 25 μg qod of Levothyroxine Sodium Tablets (Letrox®) was tried and increased gradually up to 75 μg daily. Since then liver enzymes have remained within normal range. The main difference of additive for both tablets is whether it contains lactose or not: Euthyrox® contains lactose which caused no liver injury, thus excluding the possibility that an additive of Euthyrox® contributed to liver injury. The relatively quicker and larger replacement with synthetic T4 for hypothyroidism inducing transient thyrotoxicosis was suspected, although thyroid function was normal. Immune-mediated drug-induced liver injury (DILI) was also not excluded. This is a rare case of drug-induced liver injury due to levothyroxine tablets. It reminded us that when replacement with synthetic T4 for hypothyroidism is done, smaller-dose initiation and slower-speed increase may be useful for treatment of cases similar to genetically susceptible individuals.
Center-specific variations of thyroid hormone serum levels in hemodialysis patients. [2018]Thyroid hormone (free and total thyroxine, total 3,5,3'- and 3,3'5'-triiodothyronine, thyroxine-binding globulin, thyrotropin) serum concentrations were measured in 107 uremic patients of 4 hemodialysis centers, in order to study the prevalence of hypothyroidism in hemodialysis patients. In accordance with the clinical impression there was no laboratory evidence of thyroid dysfunction. In spite of the fact that all patients had the expected low-T3 syndrome, there were highly significant differences between the mean thyroid hormone concentrations of the 4 different centers. The center with the highest thyroid hormone levels (all normal except for borderline low 3,5,3'-triiodothyronine) also had the lowest urea levels, indicating the relatively best metabolic control. One center had significantly lower hormone levels than the other 3 centers (all hormones except free thyroxine were below normal) with urea levels that did not differ significantly from one of these centers. A retrospective analysis of patients and of the techniques of dialysis of 3 centers excluded factors like heparin or the length of time on dialysis to be the reason for the low values of this center. Finally, only the significantly higher proportion of unsuccessfully transplanted patients and some technical differences (lack of water treatment, regenerated cellulose as dialyser membrane, and low magnesium content in the dialysate) unique for this center remained as possible factors that may speculatively explain the observed low thyroid hormone values.(ABSTRACT TRUNCATED AT 250 WORDS)
Changes in thyroxine requirements in patients with hypothyroidism undergoing renal transplantation. [2013]Hypothyroidism is common in the renal failure population and is both influenced by the onset of renal failure and its correction with renal transplantation. We report a series of 20 consecutive patients on oral thyroxine, in which restoration of renal function following transplantation resulted in reduced thyroxine requirements. We speculate that iodide excess, reduced bioavailability, and drug interactions may have contributed both to their hypothyroidism and the increased requirements for thyroxine in these patients while on dialysis. Failure to recognize the changes following renal transplantation may result in significant morbidity.