Clinical trial NCT05313477: The Effects of Vitamin D and Calcium Supplementation to Parathyroid Hormone in CHB Patients Treated With TDF
Official title: The Effects of Vitamin D and Calcium Supplementation to Parathyroid Hormone in CHB Patients Treated With Tenofovir Disoproxil Fumarate
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Parathyroid Hormone
Tenofovir Disoproxil Fumarate
Chronic Hepatitis B Virus
Vitamin D
Keywords: Tenofovir disoproxil fumarate
Tenofovir
Chronic hepatitis B
Parathyroid hormone
Bone mineral density
Renal phosphate loss
Vitamin D
Calcium
TDF
PTH
CHB
HBV
Lead sponsor: Mahidol University
Sponsor class: OTHER
First posted: 2022-04-06
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in serum parathyroid hormone
timeFrame: 48weeks
Secondary outcomes:
measure: Change in bone mineral density
timeFrame: 48weeks
measure: Renal function changes
timeFrame: 48weeks
measure: Change in renal phosphate loss
timeFrame: 48weeks
Other outcomes:
Locations:
city: Bangkok
country: Thailand
facility: Faculty of Medicine, Siriraj Hospital
Study officials:
affiliation: Mahidol University
name: Watcharasak Chotiyaputta, Asso Prof
role: PRINCIPAL_INVESTIGATOR
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