Clinical trial NCT03598556: Preventing Bone Loss Among Chinese Patients With HIV on ART
Official title: Strategies for the Prevention of Bone Loss Among Patients With HIV on Antiretroviral Therapy in China
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: HIV/AIDS
Osteoporosis
Bone Loss
Keywords: China
Anti-retroviral Therapy
Vitamin D
Tenofovir
Efavirenz
Lamivudine
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
Collaborators: name: Beijing YouAn Hospital
name: Beijing Ditan Hospital
name: Guangxi Autonomous Region Longtan Hospital
name: Fuzhou Infectious Diseases Hospital
name: Shenzhen Third People's Hospital
name: Yale University
First posted: 2018-07-26
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The major goal of this study will be to conduct a randomized, double-blind, placebo-controlled, clinical trial of intermittent high-dose vitamin D3 supplementation (180,000IU) given at the point of care (every 3 months) after initiation of ART with tenofovir/ lamivudine/ efavirenz to compare its ability to mitigate reductions in bone mineral density over 12 months compared to placebo.

Detailed description: Studies among adult and pediatric populations have suggested vitamin D supplementation may be efficacious for mitigating the bone loss seen with tenofovir-based antiretroviral therapy (ART). Because patients with HIV face significant pill burden, competing priorities and health care associated costs, we seek to explore a pragmatic approach to prevention. The investigators propose a randomized controlled, double-blind, placebo intervention trial to assess the efficacy, tolerability, and safety of an intermittent high-dose vitamin D3 supplementation regimen given quarterly at the point of care for adult patients receiving free ART through the China National Free AIDS Treatment Program. The period of supplementation will be limited to the first 48 weeks after treatment initiation when ART-associated bone loss is most pronounced. This will be followed by supplementation of all participants with vitamin D3 from 48 to 96 weeks to compare the impact of early vitamin D3 supplementation (at ART initiation) versus late vitamin D3 supplementation (at 48 weeks) on change in BMD.

Furthermore, despite the rapid rise in access to ART in China, infrastructure to diagnose and manage osteoporosis is not always easily accessible for patients with HIV in China due to limited availability of dual-energy x-ray absorptiometry (DXA), the gold standard for BMD measurement. Therefore, the current proposal also seeks to bridge this gap by exploring the potential applications of quantitative ultrasound (QUS), a portable and low-cost method of assessing BMD that has been demonstrated to reliably predict fracture, in HIV care settings.

A total of 400 treatment-naïve Chinese adults diagnosed with HIV from 3 study sites in Beijing will be enrolled and followed with serial DXA exams to evaluate the primary aim. These 400 patients plus another 200 participants from 3 additional study sites from Fuzhou, Shenzhen, and Guangxi province, will be evaluated with serial QUS ultrasound examinations for the secondary aims. Serum and urine samples will be collected and stored at pre-specified time points.

Eligibility criteria: Inclusion Criteria:

* Provision of signed and dated informed consent form
* Willingness and availability to engage in study activities for the duration of the study
* Documented HIV-1 infection (confirmed by Western blot)
* ART naïve at the time of enrollment
* Eligible to initiate ART (TDF/3TC/EFV) within 1 month
* Ability to take oral medication and be willing to adhere to the mediation regimen
* For females of reproductive potential: use of highly effective contraception

Exclusion Criteria:

* Pregnancy or breastfeeding
* AIDS-defining illness within 2 weeks of entry
* Liver disease (transaminase and alkaline phosphatase levels more than three times the upper limit of the normal range (ULN), bilirubin level more than 2.5 times the ULN)
* Chronic kidney disease (serum creatinine level more than 1.5 times the ULN)
* Patients with a history of injection drug usage
* Known history of osteoporosis, osteoporotic fracture, or other metabolic/inherited bone disorder
* History of treatment with prescription therapies for osteoporosis (for example: bisphosphonates, denosumab, teriparatide, selective estrogen receptor modifying agents, active forms of vitamin D).
* Unwillingness to discontinue previous vitamin D supplementation, if any, at time of enrollment
* Rheumatoid arthritis
* Malabsorption or inflammatory bowel disease
* Hyperparathyroidism, hypercalcemia, or hypocalcemia
* History of kidney stones
* Poorly controlled thyroid disease
* History of neuromuscular disorder/movement disorder, stroke or seizures
* History of significant neurocognitive disorders (including mental health conditions or dementia)
* Glucocorticoids, estrogen, testosterone, or anticonvulsant use within the past six months

Primary outcomes:
measure: Change in Bone Mineral Density (BMD)
timeFrame: Baseline to week 48
Secondary outcomes:
measure: Immediate vs. Delayed Vitamin D3 Supplementation
timeFrame: Weeks 48 to 96
measure: Change in Quantitative Ultrasound (QUS) Measures
timeFrame: Baseline to 96 weeks
measure: Change in Biochemical Markers
timeFrame: Baseline to 96 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Ditan Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Youan Hospital
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Fuzhou
country: China
facility: Fuzhou Infectious Diseases Hospital
state: Fujian
city: Shenzhen
country: China
facility: Shenzhen Third Hospital
state: Guangdong
city: Liuzhou
country: China
facility: Longtan Hospital
state: Guangxi Autonomous Region
Study officials:
affiliation: Peking Union Medical College Hospital
name: Taisheng Li, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: