Clinical trial NCT03648528: Cholecalciferol Supplementation Effect on Parathyroid Hormone in Hemodialysis Patients
Official title: Randomized Clinical Trial for The Evaluation of The Effects Of Cholecalciferol Supplementation On The Parathyroid Hormone In Hemodialysis Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Vitamin D Deficiency
Hemodialysis Patient
Keywords: Vitamin D Deficiency
hyperparathyroidism
hemodialysis
Lead sponsor: Cooperativa Asistencia Sindicato Médico Uruguay
Sponsor class: OTHER
First posted: 2018-08-27
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double blind clinical trial in two arms
Primary purpose: TREATMENT

Brief summary: Introduction. Vitamin D regulates mineral metabolism. Its deficiency has been associated with diabetes, cancer and increased mortality. 25OH vitamin D (25VD) is stable and suitable for the evaluation of vitamin D sufficiency.

The aim of the study is to evaluate whether cholecalciferol supplementation for a period of 12 weeks can normalize decreased 25VD levels and reduce increased parathormone (iPTH) in hemodialysis (HD) patients with a vitamin D deficiency. Secondary aims: to evaluate decrease in inflammation, anemia or use of erythropoietin.

Design. Randomized, double blind clinical trial in two arms of HD patients with 25OH Vitamin D deficiency and secondary hyperparathyroidism, for a period of 12 weeks.

Population. Patients over 18 years of age on HD for more than 3 months and levels of 25VD \< 30 ng / ml and iPTH \>300 ng/ml , who sign a consent form. Randomization will be achieved by using a table of random numbers at the pharmacy, and neither doctors nor patients will know which group they have been assigned to.

Treatment. Supplementation will consist of one 5000 IU cholecalciferol tablet or placebo during dialysis for a period of 12 weeks.

Monthly monitoring will include: haemoglobin (g/dl), Calcium (mg/dl), Phosphorous (mg/dl), PTH (ng/ml), epo dose (IU/kg/week), epo resistance (IU/kg/week/g Hb).

At the beginning and end of the study the following will be measured: alkaline Phosphatase (IU/ml), PCR (mg/L), 25VD (ng/ml), ferritin (ng/ml) and transferrin saturation, quality of life (SF36).

During the study, doses of calcitrol or paricalcitol will not be modified. The study will be discontinued if calcemia ≥ 10.5 mg/dL is detected on two occasions.

Size of sample is estimated at 120 patients for a PTH decrease of 20% in 35% of patients in group treated (assuming 15% follow-up losses). Analysis will be done for Intention to treat for the primary outcome.

Ethical aspects: Authorization has been obtained from the Ethics Committee of the institution as regards Good Clinical Practices, Helsinki Declaration and national regulations. The trial will be registered at the Ministry of Health.

Detailed description: Introduction. Vitamin D regulates mineral metabolism. Its deficiency has been associated with diabetes, cancer and increased mortality. 25OH vitamin D (25VD) is stable and suitable for the evaluation of vitamin D sufficiency.

The aim of the study is to evaluate whether cholecalciferol supplementation for a period of 12 weeks can normalize decreased levels of 25VD and reduce increased parathormone (iPTH) in hemodialysis (HD) patients with a vitamin D deficiency. Secondary aims: to evaluate decrease in inflammation, anemia or use of erythropoietin (epo).

Design. Randomized, double blind clinical trial in two arms of HD patients with 25VD deficiency and secondary hyperparathyroidism, one arm to be treated with cholecalciferol supplementation and the other with a placebo, for a period of 12 weeks.

Population. Patients over 18 years of age on HD for more than 3 months and levels of 25VD \< 30 ng / ml and iPTH \>300 ng/ml , who sign a consent form. Once their consent has been obtained, iPTH and 25VD levels will be measured. Randomization will be achieved by using a table of random numbers at the pharmacy, and neither doctors nor patients will know which group they have been assigned to.

Treatment. Supplementation will consist of three 5000 IU cholecalciferol tablets or placebo postdialysis per week during dialysis for a period of 12 weeks.

Monthly monitoring will include: haemoglobin (g/dl), Calcium (mg/dl), Phosphorous (mg/dl), iPTH (ng/ml), epo dose (IU/kg/week), epo resistance (IU/kg/week/g Hb).

At the beginning and end of the study the following will be measured: alkaline Phosphatase (IU/ml), C reactive protein (mg/L), 25VD (ng/ml), ferritin (ng/ml) and transferrin saturation, quality of life (SF36).

During the study, doses of calcitrol or paricalcitol will not be modified. The study will be discontinued if calcemia ≥ 10.5 mg/dL is detected on two occasions.

Size of sample is estimated at 120 patients for a iPTH decrease of 20% in 35% of patients in group treated (assuming 15% follow-up losses). Analysis will be done for Intention to treat for the primary outcome.

Ethical aspects: Authorization has been obtained from the Ethics Committee of the institution as regards Good Clinical Practices, Helsinki Declaration and national regulations. The trial was registered at the Ministry of Health.

Eligibility criteria: Inclusion Criteria:

* Age 18 or over
* signed informed consent form
* ESRD with regular dialysis treatment for at least 3 months
* levels of 25VD \< 30 ng / ml
* levels of iPTH \>300 ng/ml,
* stable doses of calcitrol or paricalcitol over the last 30 days.

Exclusion Criteria:

* Congestive heart failure class III or IV
* unstable angina or myocardial infarction or stroke during the previous 3 months
* active malignant neoplasm
* use of any trial medication
* life expectancy lower than 6 months
* corrected calcemia ≥ 10.5 in the 2 months prior to recruitment
* intake of cholecalciferol or ergocalciferol in the 2 months prior to recruitment
* prospective move to another city or transfer to PD in the following 6 months.

Primary outcomes:
measure: 20 % Change in iPTH levels
timeFrame: 12 weeks
measure: normalization of 25VD levels
timeFrame: 12 weeks
Secondary outcomes:
measure: change of 0.5 g/dL on Hb level or 10% change in erythropoietin dose
timeFrame: 12 weeks
Other outcomes:
Locations:
Study officials:
References: