Clinical trial NCT03898622: Supplementation of Thyroid Hormone for TSH Control in Patients With Chronic Kidney Disease Without TRR.
Official title: Supplementation of Thyroid Hormone for TSH Control in Patients With Chronic Kidney Disease Without Renal Replacement Therapy: Randomized, Double-blind Clinical Trial at Guadalajara Civil Hospital.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Kidney Diseases
Subclinical Hypothyroidism
Lead sponsor: Hospital Civil de Guadalajara
Sponsor class: OTHER
First posted: 2019-04-02
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase II study, type placebo controlled clinical trial, randomized of two arms, double blind, unicentric.
Primary purpose: TREATMENT

Brief summary: Study design: Phase II study, randomized, double-blind, unicentric, two-arm, placebo-controlled clinical trial. Methods and participants: Patients with Chronic Kidney Disease G2-G5 with proteinuria without renal replacement therapy, who come to the clinic of renal health clinic of the Fray Antonio Alcalde civil hospital. As criteria for non-inclusion, need for dialysis, primary hypothyroidism or pre-existing thyroid disease, ischemic heart disease in a period less than 6 months, arrhythmia, pregnancy, use of drugs that interact with synthesis of thyroid hormones, do not accept informed consent, thyroid stimulating hormone (TSH) \<2.5 uiml / L or TSH\> 10 uiml / L.

Detailed description: Thyroid disorders, especially elevated TSH levels in patients with CKD, are frequent. As it is an easy medication to acquire and of little cost compared to the other options, levothyroxine would provide benefits already known in patients with CKD and also a proteinuria effect (knowing each other). as a factor of progression of the CKD a health problem worldwide) being a potentially useful treatment and a dose that the risk is minimal. The study consists of 3 phases, the first phase consists of capturing patients from the renal health clinic, having baseline measurement of the variables. Then, the second phase consists of both groups treating them with medication (levothyroxine with a safe dose for the investigator's population with high cardiovascular risk of 0.25mcg so that the patient's weight range between 50-80kg maintains a dosage of 0.3-0.5mcg / kg / day that the thyroid axis is not affected) of fasting levothyroxine (in the case of taking a drug that interacts with absorption changes its use according to the specified hours, see Table 2) or placebo according to the randomization 1: 1 for three months and that have treatment with ACEI or ARA-2 (specifying which and the dose thereof), with follow-up every 4 weeks (Monitoring thyroid function). The third phase consists of a comparison of the variables studied.

The primary objective is to evaluate the effect of the use of levothyroxine on the levels of proteinuria measured on the test strip of the general urine and protein examination in 24-hour urine patients with chronic kidney disease without renal support therapy with proteinuria, who already receive the standard antiproteinuric treatment with an ACE inhibitor or ARA-2 against placebo and the secondary objectives are to evaluate the changes in proteinuria, according to TSH levels in 2.5-9.9 μiml /L, with the levels of T4L in levels 0.8-1.8mcg / ml), analyze improvement in glomerular filtration rate in patients receiving levothyroxine and at the end of the study and evaluate Tolerability and safety of levothyroxine as antiproteinuric treatment in chronic kidney disease without renal support therapy, and as secondary objectives improvement in cholesterol, triglycerides blood pressure. Any adverse event will be recorded in the adverse event reporting forms. (definition of the International Conference on Harmonization \[ICH\])

Eligibility criteria: Inclusion Criteria:

* • Patients older than 18 years

  * Patients with chronic kidney disease G2-G5 without renal replacement therapy) who attend a renal health clinic.
  * Presence of proteinuria in a test strip, 24 hours urine collection (greater than 150mg / dl in 24hrs urine)
  * TSH \<9.9uiml / L and TSH\> 2.4 0uiml / L
  * Take an IECA or ARA-2
  * Patients with weight\> 50 kg and \<80kg
  * Accept informed consent

Exclusion Criteria:

* Chronic dialysis (peritoneal dialysis or hemodialysis)

  * Primary hypothyroidism or preexisting thyroid disease
  * Use of levothyroxine.
  * TSH\> 10uiml / L and TSH \<2.5 0uiml / L
  * Positive thyroid antibodies
  * Ischemic heart disease in less than 6 months
  * Cardiac arrhythmia
  * Use Medications (Levothyroxine synthesis, see Table 2)
  * Anxiety disorder
  * Pregnancy
  * Do not accept consent
  * Patients weighing \<50 kg and\> 80kg

Primary outcomes:
measure: 24 hours urine Proteinuria in patients with subclinical hypothyroidism and CKD G2-G5 without renal support therapy Randomized clinical trial of levothyroxine group versus placebo
timeFrame: three months
Secondary outcomes:
measure: Estimated glomerular filtration rate (eGFR) in patients with subclinical hypothyroidism and CKD G2-G5 without renal support therapy Randomized clinical trial of levothyroxine group versus placebo
timeFrame: three months
measure: Measurement of lipid profile (cholesterol, LDL and triglycerides) in patients with subclinical hypothyroidism and CKD G2-G5 without renal support therapy Randomized clinical trial of levothyroxine group versus placebo.
timeFrame: three months
Other outcomes:
measure: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) when using levothyroxine in patients with subclinical hypothyroidism and CKD
timeFrame: four months
Locations:
city: Guadalajara
country: Mexico
facility: Kidney health clinic, Civil Hospital of Guadalajara
state: Jalisco
Study officials:
affiliation: Hospital Civil de Guadalajara
name: Jonathan Chavez
role: STUDY_DIRECTOR
References: