The Effects of Vitamin D and Calcium Supplementation to Parathyroid Hormone in CHB Patients Treated With TDF (TDF)

February 7, 2024 updated by: Watcharasak Chotiyaputta, Mahidol University

The Effects of Vitamin D and Calcium Supplementation to Parathyroid Hormone in CHB Patients Treated With Tenofovir Disoproxil Fumarate

Nucleot(s)ide is an antiviral drug that can reduce the number of viruses, reduce the risk of HCC, regress hepatic fibrosis and reduce death from Hepatitis B viral infection. Tenofovir disoproxil fumarate (TDF) is one of nucleotide analogue that is recommended to treated patients with Hepatitis B viral infection. However, long-term TDF therapy may have side effects especially nephrotoxicity and bone toxicity.

Previous studies in human immunodeficiency virus (HIV) infected patients who treated with TDF containing regimen antiretroviral therapy, in vitamin D supplement group had a statistic significance of low parathyroid hormone level and better in bone mineral density regardless of initial vitamin D level. Therefore, the main objective of this study is to evaluate the vitamin D and calcium supplement to patients with hepatitis B who have taken TDF, in parathyroid hormone level, bone mineral density, renal function and renal phosphate loss compared to patients who have no vitamin D and calcium supplement.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Hepatitis B virus is a global public health problem. This infection leads to chronic hepatitis, cirrhosis and liver cancer. According to past statistics, infection with hepatitis B virus is a common cause of hepatocellular carcinoma about 60% in East-Asia and Africa and about 20% in Western countries. About 350-400 million people are infected worldwide. Infection with hepatitis B virus is also an important factor of death in 1million patients per year.

Nucleot(s)ide is an antiviral drug that can reduce the number of viruses, reduce the risk of HCC, regress hepatic fibrosis and reduce death from Hepatitis B viral infection. Nowadays, the recommendation of nucleot(s)ide prefers Tenofovir disoproxil fumarate (TDF), Tenofovir Alafenamide (TAF) and Entecavir (ETV) than Lamivudine, Adefovir and Telbivudine due to high potency and low resistance rate Tenofovir disoproxil fumarate (TDF) is one of nucleotide analogue that inhibits reverse transcriptase in HBV replication process. However, long-term TDF therapy may have side effects especially nephrotoxicity. The proposed mechanisms of nephrotoxicity of TDF are cumulative of TDF at proximal tubule of kidney leads to mitochondrial toxicity, downregulation of sodium-phosphorus cotransporter, sodium/ hydrogen exchanger 3 and aquaporin 2, decreased endothelial nitric oxide-synthase (eNOS) and renal vasoconstriction results in tubulopathy in renal proximal tubule, increase of phosphate loss in urine and increase od serum creatinine.

Moreover, TDF also affects to decrease bone mineral density (BMD) that related with renal phosphate loss, loss of osteoblast function, high parathyroid hormone level regardless of vitamin D level and high fibroblast growth factor 23 (FGF23) leads to worsen in bone mineralization Vitamin D has a protective effect and indicate for osteoporosis treatment. The chronic hepatitis B infected patients with vitamin D deficiency may have a poor prognosis in hepatic fibrosis and high HBV DNA level. Previous studies in human immunodeficiency virus (HIV) infected patients who treated with TDF containing regimen antiretroviral therapy, in vitamin D supplement group had a statistic significance of low parathyroid hormone level and better in bone mineral density regardless of initial vitamin D level. Therefore, the main objective of this study is to evaluate the vitamin D and calcium supplement to patients with hepatitis B who have taken TDF, in parathyroid hormone level, bone mineral density, renal function and renal phosphate loss compared to patients who have no vitamin D and calcium supplement.

Study Type

Interventional

Enrollment (Actual)

64

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Thailand
      • Bangkok, Thailand, 10700
        • Faculty of Medicine, Siriraj Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Age between 18 - 75 years old
  • Chronic hepatitis B infected patients treated with TDF monotherapy
  • eGFR ≥ 60 mL/ min/ 1.73 m2
  • HBV viral load <10 IU/ mL

Exclusion Criteria:

  • HIV infection or hepatitis C co-infection
  • Decompensated cirrhosis, including variceal bleeding, ascites, hepatic encephalopathy
  • History of Hepatocellular carcinoma
  • Active malignancy of cancer in other organs
  • Pregnancy or lactation
  • Primary hyperparathyroidism
  • History of thyroid or parathyroid surgery
  • History of radiation at neck area
  • Any osteoporosis treatment or history of osteoporosis diagnosis
  • Chronic kidney disease
  • Current use of Vitamin D
  • Adverse event or allergy to TDF
  • Chronic hepatitis B patients with TDF resistance

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Supplement group

Vitamin D2 supplement based on initial vitamin D level

  • ≥ 20ng/mL -> vitamin D2 20,000unit/week
  • 10-19.9ng/mL -> vitamin D2 40,000unit/week
  • <10ng/mL -> vitamin D2 60,000unit/week Calcium carbonate 1000mg/day
Drug: Ergocalciferol Capsules
Depend on initial 25(OH) vitamin D level If <10ng/mL, 60000U of Ergocalciferol capsules per week If 10-19.9ng/mL, 40000U of Ergocalciferol capsules per week If >20 ng/mL, 20000U of Ergocalciferol capsule per week
Drug: Calcium carbonate
1000mg of Calcium carbonate daily
No Intervention: No supplement group
no medication supplement

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in serum parathyroid hormone
Time Frame: 48weeks
Change from the baseline in serum parathyroid hormone as assessed by Electrochemiluminescent immunoassay (ECLIA)
48weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in bone mineral density
Time Frame: 48weeks
Change from the baseline in bone mineral density as assessed by Dual-energy X-ray absorptiometry (DXA)
48weeks
Renal function changes
Time Frame: 48weeks
Change from the baseline in renal function (eGFR) based on creatinine as assessed by Enzymatic method
48weeks
Change in renal phosphate loss
Time Frame: 48weeks
Change from the baseline in the tubular reabsorption of phosphate (TRP) as renal phosphate loss depended on serum creatinine, urine creatine (assessed by enzymatic method) and serum phosphate, urine phosphate (assessed by modification of the classical phosphomolybdate method by Fiske and Subbarow)
48weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mahidol University

Investigators

  • Principal Investigator: Watcharasak Chotiyaputta, Asso Prof, Mahidol University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2022

Primary Completion (Actual)

August 31, 2023

Study Completion (Actual)

November 30, 2023

Study Registration Dates

First Submitted

March 7, 2022

First Submitted That Met QC Criteria

March 28, 2022

First Posted (Actual)

April 6, 2022

Study Record Updates

Last Update Posted (Estimated)

February 9, 2024

Last Update Submitted That Met QC Criteria

February 7, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Si 1045/2020

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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