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

Must not be taking: Thyroid hormones, Anti-thyroid

Disqualifiers: Kidney transplant, Malignancy, Pregnancy, others

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. ^{1 2 3 4 5}

Is 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. ^{1 6 7 8 9}

How 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. ^{1 3 5 10 11}

Research Team

Eligibility 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.

Have ability to provide written informed consent

I have been on hemodialysis for at least four weeks.

Exclusion Criteria

I am currently taking medication for my thyroid condition.

I am currently on dialysis.

I am currently experiencing worsening heart failure symptoms.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive levothyroxine or placebo for 24 weeks with dose titrations at 8 and 16 weeks based on TSH levels

24 weeks

Regular visits for dose titration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Levothyroxine Sodium (Hormone Therapy)
• Placebos (Other)

Trial Overview 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.

Participant Groups

Group I: Levothyroxine Experimental Treatment 1 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: Placebo Placebo Group 1 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 Canada, Japan, China, Switzerland for the following indications:

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

Who Is Running the Clinical Trial?

University of California, Irvine

Lead Sponsor

Trials

580

Recruited

4,943,000+

Chad T. Lefteris

University of California, Irvine

Chief Executive Officer since 2019

MBA from University of California, Irvine

Michael J. Stamos

University of California, Irvine

Chief Medical Officer since 2019

MD, PhD from University of California, Irvine

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Dr. Griffin P. Rodgers

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Chief Executive Officer since 2007

MD, M.A.C.P.

Dr. Griffin P. Rodgers

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Chief Medical Officer since 2007

MD, M.A.C.P.

Findings from Research

Levothyroxine sodium treatment effectively prevented progressive renal failure in a 49-year-old female patient with diabetes and hypothyroidism over a period of more than 24 months.

Before treatment, the patient's renal function worsened, as indicated by a negative slope in serum creatinine levels, which improved to a positive slope after starting levothyroxine, suggesting its efficacy in stabilizing renal function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention of progressive renal failure by levothyroxine sodium in a diabetic patient with renal insufficiency and hypothyroidism. Miura, M., Nomoto, Y., Sakai, H.[2019]

In a study of 200 patients with stage 3-4 chronic kidney disease (CKD), treatment with levothyroxine improved nutritional indicators such as weight, grip strength, hemoglobin, and serum albumin compared to a control group.

Levothyroxine treatment also led to an increase in estimated glomerular filtration rate (eGFR) in the treatment group, indicating a delay in kidney disease progression, particularly more effective in patients with stage 3 CKD than in those with stage 4.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FAVORABLE EFFECT OF LEVOTHYROXINE ON NUTRITIONAL STATUS OF PATIENTS WITH STAGE 3-4 CHRONIC KIDNEY DISEASE. Tang, W., Chen, Q., Chen, L., 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]

Levothyroxine (LT4) therapy significantly reduced urinary albumin excretion rate (UAER) and improved cholesterol levels in 136 patients with early type 2 diabetic nephropathy and subclinical hypothyroidism after 48 weeks of treatment.

The study suggests that LT4 may offer kidney protection in these patients, but further research with larger sample sizes and longer follow-up is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Liu, P., Liu, R., Chen, X., et al.[2018]

A 71-year-old female patient with end-stage renal disease and uncontrolled hypothyroidism was successfully treated with intravenous (IV) levothyroxine during hemodialysis sessions after refusing oral and intramuscular forms of the medication.

The patient's thyroid function normalized within 19 weeks of starting IV levothyroxine, leading to a resolution of her psychosis, highlighting the efficacy of this unconventional treatment approach when standard methods are not feasible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

INTRAVENOUS LEVOTHYROXINE DURING HEMODIALYSIS IN A PATIENT WITH HYPOTHYROIDISM AND NON-ADHERENCE TO ORAL MEDICATIONS. Avichal, D., Kravets, I.[2022]

In a study of 3965 adult patients using levothyroxine (LT4), those taking oral liquid formulations showed greater variability in thyroid stimulating hormone (TSH) levels compared to tablet users, indicating potential differences in absorption or metabolism.

During drug-drug interactions (DDIs), patients using oral liquid LT4 had less increase in prescribed daily dosages (PDDs) compared to those using tablets, suggesting that liquid formulations may be more stable in complex therapeutic regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug interactions in users of tablet vs. oral liquid levothyroxine formulations: a real-world evidence study in primary care. Guglielmi, V., Bellia, A., Bianchini, E., et al.[2019]

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]

Levothyroxine sodium is the preferred treatment for most patients with hypothyroidism, providing stable hormone levels without daily fluctuations, and optimal dosing is guided by maintaining a TSH level of 1-2 mU/L.

In younger patients, starting with a near full dose of levothyroxine is effective, while older patients or those with coronary artery disease should begin with a lower dose to minimize risks of cardiac events and osteoporosis from over-replacement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing treatment of hypothyroidism. Clarke, N., Kabadi, UM.[2019]

A 49-year-old woman with hypothyroidism experienced liver dysfunction after increasing her levothyroxine dose, which was resolved after stopping the medication, indicating a case of levothyroxine-induced liver injury.

Switching to a different levothyroxine formulation (Letrox®) without lactose and gradually increasing the dose helped maintain normal liver enzyme levels, suggesting that careful dosing and formulation choice are important in preventing drug-induced liver injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liver dysfunction induced by Levothyroxine Sodium Tablets (Euthyrox®) in a hypothyroid patient with Hashimoto's thyroiditis: case report and literature review. Yu, H., Zhang, W., Shen, C., et al.[2020]

In a study of 20 patients undergoing renal transplantation, it was found that restoring kidney function led to a significant reduction in their need for oral thyroxine, a medication used to treat hypothyroidism.

The study suggests that factors like iodide excess and drug interactions during dialysis may have contributed to both the hypothyroidism and the increased thyroxine requirements, highlighting the importance of monitoring thyroid function after transplantation to prevent potential health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in thyroxine requirements in patients with hypothyroidism undergoing renal transplantation. Thomas, MC., Mathew, TH., Russ, GR.[2013]

References

1. Japan pubmed.ncbi.nlm.nih.gov

Prevention of progressive renal failure by levothyroxine sodium in a diabetic patient with renal insufficiency and hypothyroidism. [2019]

2. Romania pubmed.ncbi.nlm.nih.gov

FAVORABLE EFFECT OF LEVOTHYROXINE ON NUTRITIONAL STATUS OF PATIENTS WITH STAGE 3-4 CHRONIC KIDNEY DISEASE. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

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

4. England pubmed.ncbi.nlm.nih.gov

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]

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

INTRAVENOUS LEVOTHYROXINE DURING HEMODIALYSIS IN A PATIENT WITH HYPOTHYROIDISM AND NON-ADHERENCE TO ORAL MEDICATIONS. [2022]

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

Drug interactions in users of tablet vs. oral liquid levothyroxine formulations: a real-world evidence study in primary care. [2019]

7. France pubmed.ncbi.nlm.nih.gov

[Treatment of hypothyroidism]. [2013]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Optimizing treatment of hypothyroidism. [2019]

9. Japan pubmed.ncbi.nlm.nih.gov

Liver dysfunction induced by Levothyroxine Sodium Tablets (Euthyrox®) in a hypothyroid patient with Hashimoto's thyroiditis: case report and literature review. [2020]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Center-specific variations of thyroid hormone serum levels in hemodialysis patients. [2018]

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

Changes in thyroxine requirements in patients with hypothyroidism undergoing renal transplantation. [2013]