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

Vitamin D Clinical Trial

— TDF  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05313477
• Other study ID #: Si 1045/2020
• Status: Completed
• Phase: Phase 4
• Start date: May 1, 2022
• Est. completion date: November 30, 2023

Study information

• Verified date: February 2024
• Source: Mahidol University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: November 30, 2023
• Est. primary completion date: August 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Hepatitis B Virus
• Hepatitis
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic
• Parathyroid Hormone
• Tenofovir Disoproxil Fumarate
• Vitamin D

Intervention

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
• Calcium carbonate
1000mg of Calcium carbonate daily

Locations

Country	Name	City	State
Thailand	Faculty of Medicine, Siriraj Hospital	Bangkok

Sponsors (1)

Lead Sponsor	Collaborator
Mahidol University

Country where clinical trial is conducted

Thailand, 

References & Publications (32)

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* Note: There are 32 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in serum parathyroid hormone	Change from the baseline in serum parathyroid hormone as assessed by Electrochemiluminescent immunoassay (ECLIA)	48weeks
Secondary	Change in bone mineral density	Change from the baseline in bone mineral density as assessed by Dual-energy X-ray absorptiometry (DXA)	48weeks
Secondary	Renal function changes	Change from the baseline in renal function (eGFR) based on creatinine as assessed by Enzymatic method	48weeks
Secondary	Change in renal phosphate loss	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