A Study on Prevention Strategies for CKD-SHPT and Related Complications Based on General Vitamin D Supplementation

1. Study content: This is a multicentre, double-blind, randomised controlled study to determine the optimal dose and duration of treatment for the correction of vitamin D insufficiency or deficiency in patients with CKD5d; to investigate whether vitamin D supplementation delays the increase in PTH levels in this group of patients; and to investigate the effects on changes in CKD-MBD-related markers, cardiovascular complications, cognitive function in this group of patients. 2. Study procedure: Based on the inclusion and exclusion of the patients, the study was conducted in accordance with the following criteria
2. Study procedure: Eligible subjects were screened according to inclusion and exclusion criteria and randomly divided into three groups: high-dose vitamin D group, low-dose vitamin D group and control group. Baseline data were collected before the intervention and each group was given different doses of regular vitamin D2 softgels or placebo and followed up. 25(OH)D, PTH, blood Ca, and blood P levels were measured every month; bone metabolism markers, FGF23, and blood counts, liver function, kidney function, lipids, and blood glucose were measured every 3 months; the prevalence of vascular calcification, the incidence of cardiovascular events, and changes in cognitive function scale scores were assessed 6 months after the intervention.

Study Overview

• Status: Recruiting
• Conditions: Vitamin D Deficiency; Chronic Kidney Disease 5D; Secondary Hyperparathyroidism Due to Renal Causes
• Intervention / Treatment: Drug: High-dose vitamin D2 softgels; Drug: low-dose vitamin D2 softgels; Drug: placebo

• Study Type: Interventional
• Enrollment (Anticipated): 372
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hongli Jiang, Professor; Phone Number: 13700280897; Email: j92106@sina.com

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
      • Recruiting
      • The First Affiliated Hospital of Xi 'an Jiaotong University
      • Contact: Hongli Jiang; Phone Number: 13700280897; Email: j92106@sina.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 18 years.
2. Patients with chronic kidney disease stage 5d who have been on haemodialysis for 3 months or more
3. 5 ng/mL < 25(OH)D < 30 ng/mL (liquid phase tandem mass spectrometry).
4. 130 pg/ml < PTH < 600 pg/ml (electrochemiluminescence method).
5. serum phosphorus < 1.78 mmol/L.
6. Good compliance with the treatment requirements formulated for the study.
7. informed consent from the subject.

Exclusion Criteria:

1. Patients who are prepped for or have undergone renal transplantation or parathyroidectomy.
2. taking vitamin D, active vitamin D or analogues and other drugs that may affect 25(OH)D levels within 3 months prior to enrolment
3. Treatment affecting PTH results (e.g. cenacaser, etc.) within 3 months prior to enrolment
4. Serum calcium > 2.55 mmol/L
5. Patients who are pregnant or likely to become pregnant, breastfeeding or planning to become pregnant during the study period
6. known prior or concomitant serious illness or medical condition such as malignancy, human immunodeficiency virus, severe gastrointestinal or liver disease, intestinal malabsorptive disease, hepatitis or cardiovascular events that may worsen or shorten life expectancy and/or interfere with participation in the study
7. History of neurological/psychiatric disease, including psychosis or dementia, or any other reason that is unlikely to result in adherence to treatment or follow-up plans.
8. Known or suspected allergy to any component of the study drug.
9. Ongoing participation in other clinical studies.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control group; Placebo	Drug: placebo; placebo was filled with excipients (aniseed ether, refined vegetable oil), and the shape and size were the same as vitamin D2 soft capsule.the control group was given placebo, 5 placebo capsules twice weekly for 6 months of the intervention. The medication was dispensed by a designated person (not the investigator) in advance and independently according to the patient's medication number (only the drug number was provided on the outer packaging).
Experimental: High-dose vitamin D group; Vitamin D2 softgels 50,000 U/week	Drug: High-dose vitamin D2 softgels; 5000U/capsule of vitamin D2 soft capsule; High-dose VD group 50,000 U/week, 5 vitamin D2 softgels given twice a week each time; 25(OH)D > 80ng/ml after 3 months of intervention or within 3 months in both groups, changed to 5,000 U/ weekly maintenance until the full 6 months of intervention. To prevent unmasking, the maintenance dose was still given twice weekly (the first time 1 vitamin D2 capsule + 4 placebo capsules were given and the second time 5 placebo capsules were given)
Experimental: Low-dose vitamin D group; low-dose vitamin D group	Drug: low-dose vitamin D2 softgels; 5000U/capsule of vitamin D2 soft capsule; low-dose VD group 25,000 U/week, 3 vitamin D2 softgels + 2 placebo in the first dose, 2 vitamin D2 softgels + 3 placebo in the second dose, 25(OH)D > 80ng/ml after 3 months of intervention or within 3 months in both groups, changed to 5,000 U/ weekly maintenance until the full 6 months of intervention. To prevent unmasking, the maintenance dose was still given twice weekly (the first time 1 vitamin D2 capsule + 4 placebo capsules were given and the second time 5 placebo capsules were given);

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Differences in changes in PTH levels from baseline to 6 months of intervention	baseline，at 6 months intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in changes in PTH levels from baseline to intervention at 1months、2months、3months、4months、5months		baseline，at 1，2，3，4，5 months intervention
Proportion of 25(OH)D >30ng/ml at 3 months of intervention		at 3 months intervention
Trends in changes in 25(OH)D levels from baseline to intervention at 1months、2months、3months、4months、5months、6months		baseline，at 1，2，3，4，5，6 months intervention
Incidence of cardiovascular events after 6 months of intervention		baseline，at 6 months intervention
Change in prevalence of vascular calcification at 6 months of intervention	We used cardiac ultrasound and lateral abdominal views to look for vascular calcification	baseline，at 6 months intervention
Change in Montreal Cognitive Assessment Scale scores at 6 months of intervention	A total score of 30 on this scale, with a score of ≥26 indicating normal; a score of <26 indicates the presence of cognitive impairment: 18-26 for mild cognitive impairment, 10-17 for moderate cognitive impairment and <10 for severe cognitive impairment	baseline，at 6 months intervention
Trends in blood calcium levels at 1 month, 2 months, 3 months, 4 months, 5 months and 6 months of intervention		baseline，at 1，2，3，4，5，6 months intervention
Trends in blood phosphorus levels at 1 month, 2 months, 3 months, 4 months, 5 months and 6 months of intervention		baseline，at 1，2，3，4，5，6 months intervention
Trends in FGF23 levels at 3 and 6 months of intervention		baseline，at 3，6 months intervention
Trends in Osteocalcin(OC) levels at 3 and 6 months of intervention		baseline，at 3，6 months intervention
Trends in Precollagen type I amino-terminal peptide(PINP) levels at 3 and 6 months of intervention		baseline，at 3，6 months intervention
Trends in β specific collagen degradation products(β-CTX) levels at 3 and 6 months of intervention		baseline，at 3，6 months intervention
Trends in ALP levels at 3 and 6 months of intervention		baseline，at 3，6 months intervention
Incidence of fractures at 6 months of intervention	Ask if the patient had a fracture during the intervention, the site of the fracture and the type of fracture	baseline，at 6 months intervention
Incidence of falls at 6 months of intervention	Ask if the patient has fallen during the intervention, the number of falls and the reasons for them	baseline，at 6 months intervention

Collaborators and Investigators

• Sponsor: First Affiliated Hospital Xi'an Jiaotong University

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2022
• Primary Completion (Anticipated): August 1, 2023
• Study Completion (Anticipated): October 30, 2023

Study Registration Dates

• First Submitted: September 1, 2022
• First Submitted That Met QC Criteria: September 19, 2022
• First Posted (Actual): September 22, 2022

Study Record Updates

• Last Update Posted (Estimate): January 9, 2023
• Last Update Submitted That Met QC Criteria: January 5, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Endocrine System Diseases; Renal Insufficiency; Nutrition Disorders; Parathyroid Diseases; Avitaminosis; Deficiency Diseases; Malnutrition; Kidney Diseases; Renal Insufficiency, Chronic; Hyperparathyroidism; Vitamin D Deficiency; Hyperparathyroidism, Secondary; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: XJTU1AF2022LSK-320

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The data including baseline characteristics of study population, blood biochemical index and main outcome measures may be made available.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No