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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03426592




Registration number
NCT03426592
Ethics application status
Date submitted
1/02/2018
Date registered
8/02/2018
Date last updated
5/06/2019

Titles & IDs
Public title
Effect of High Dose Vitamin D Supplementation on HIV Latency
Scientific title
Effect of High Dose Vitamin D Supplementation on HIV Latency: A Pilot Randomized Controlled Trial
Secondary ID [1] 0 0
2016.362
Universal Trial Number (UTN)
Trial acronym
VIVA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Human Immunodeficiency Virus 0 0
Condition category
Condition code
Infection 0 0 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Vitamin D3, 10000 Intl Units Oral Capsule
Treatment: Drugs - Placebo oral capsule

Active Comparator: Vitamin D3, 10000 Intl Units Oral Capsule - Vitamin D3, 10000 Intl Units Oral Capsule, daily for 6 months

Placebo Comparator: Placebo oral capsule - Oleic acid capsule by mouth, daily for 6 months


Treatment: Drugs: Vitamin D3, 10000 Intl Units Oral Capsule
Vitamin D capsule. Over-encapsulated to mimic placebo oral capsule.
Eligible study participants will be randomized 1:1 to vitamin D or placebo one capsule daily from week 0 to week 24. All participants will be advised to achieve 1 gram daily dietary calcium intake whilst on study.
Blood and urine will be taken at 0, 12, 24 and 36 weeks to evaluate the primary and secondary endpoints.
Rectal swabs will be taken at 0, 24 and 36 weeks.
All participants will continue antiretroviral therapy throughout the study.

Treatment: Drugs: Placebo oral capsule
Capsule containing oleic acid. Over-encapsulated to mimic vitamin D3 capsule.
Eligible study participants will be randomized 1:1 to vitamin D or placebo one capsule daily from week 0 to week 24. All participants will be advised to achieve 1 gram daily dietary calcium intake whilst on study.
Blood and urine will be taken at 0, 12, 24 and 36 weeks to evaluate the primary and secondary endpoints.
Rectal swabs will be taken at 0, 24 and 36 weeks.
All participants will continue antiretroviral therapy throughout the study.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in total HIV DNA level - The difference between the vitamin D and placebo arms in the mean change in frequency of total HIV DNA within CD4+ T cells from week 0 to week 24
Timepoint [1] 0 0
weeks 0 and 24
Secondary outcome [1] 0 0
Change in other DNA markers of HIV persistence - Total HIV DNA, integrated HIV DNA and 2-LTR circles in peripheral blood CD4+ T cells using PCR
Timepoint [1] 0 0
Weeks 0, 12, 24, 36
Secondary outcome [2] 0 0
Change in cell-associated HIV RNA - Cell-associated unspliced and multiply spliced HIV RNA in peripheral blood CD4+ T cells using RT-PCR and Tat/rev Induced Limiting Dilution Assay (TILDA)
Timepoint [2] 0 0
Weeks 0, 12, 24, 36
Secondary outcome [3] 0 0
Change in proportion of immune cells - T helper and T cytotoxic subsets, monocytes, dendritic cells and natural killer cells using flow cytometry
Timepoint [3] 0 0
Weeks 0, 12, 24, 36
Secondary outcome [4] 0 0
Change in T cell subset phenotype - T cell subset activation and exhaustion marker and chemokine receptor expression using flow cytometry
Timepoint [4] 0 0
Weeks 0, 12, 24, 36
Secondary outcome [5] 0 0
Change in HIV-specific immunity - HIV-specific CD4+ and CD8+ T cell frequency and polyfunctionality using HIV peptides and flow cytometry
Timepoint [5] 0 0
Weeks 0, 12, 24, 36
Secondary outcome [6] 0 0
Change in CD4+ T cell transcriptional profile - CD4+ T cell transcriptional profile using RNA Seq
Timepoint [6] 0 0
Weeks 0, 12, 24, 36
Secondary outcome [7] 0 0
Change in high sensitivity C-reactive protein (hsCRP) - hsCRP levels
Timepoint [7] 0 0
Weeks 0, 12, 24, 36
Secondary outcome [8] 0 0
Change in gut barrier permeability - Gut barrier permeability using plasma lipopolysaccharide (LPS), soluble CD14 and intestinal fatty acid binding protein (I-FABP)
Timepoint [8] 0 0
Weeks 0, 12, 24, 36
Secondary outcome [9] 0 0
Change in gut microbiome diversity - Gut microbiome diversity using 16S rRNA sequencing and metagenomics
Timepoint [9] 0 0
Weeks 0, 24, 36
Secondary outcome [10] 0 0
Change in plasma microbiome abundance and diversity - Plasma microbiome abundance and diversity using deep sequencing
Timepoint [10] 0 0
Weeks 0, 24, 36
Secondary outcome [11] 0 0
25-hydroxyvitamin D levels - Serum 25-hydroxyvitamin D levels and correlation between level achieved and each of the other endpoints (efficacy analysis)
Timepoint [11] 0 0
Weeks 0, 12, 24, 36
Secondary outcome [12] 0 0
Serum calcium levels - Serum calcium corrected for albumin
Timepoint [12] 0 0
Weeks 0, 12, 24, 36
Secondary outcome [13] 0 0
Urinary calcium levels - Urinary calcium:creatinine ratios and, where these are abnormal, 24 hour urinary calcium levels
Timepoint [13] 0 0
Weeks 0, 12, 24, 36
Secondary outcome [14] 0 0
Adverse events - Incidence and severity of adverse events
Timepoint [14] 0 0
Weeks 0, 12, 24, 36
Secondary outcome [15] 0 0
Study protocol adherence - Adherence to study drug and 1g daily dietary calcium intake as measured by pill count and participant report
Timepoint [15] 0 0
Weeks 0 to 24

Eligibility
Key inclusion criteria
- Written informed consent obtained

- At least 18 years of age

- Documented HIV-1 infection

- Receiving combination antiretroviral therapy continuously for at least 3 years

- Viral load suppressed below 40 copies/mL, or below assay limit of quantification where
limit of quantification is above 40 copies/mL, for at least 3 years (excluding single
episodes of HIV viral load 40-500 copies/mL where subsequent viral load was below 40
copies/mL or below assay limit of quantification where limit of quantification is
above 40 copies/mL)

- Viral load < 40 copies/ml at screening

- Screening 25-hydroxyvitamin D level within 12 months prior to recruitment between 50nM
and 125nM

- Agreement not to take any vitamin D containing compounds other than study drug between
screening and conclusion of the study

- Agreement not to have vitamin D level checked by a treating doctor during the study
unless medically required
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Any planned change to ART regimen within next 12 months (other than switching
tenofovir disoproxil fumarate to tenofovir alafenamide)

- Known current acute or chronic hepatitis B, known current acute or chronic hepatitis C
or positive HBsAg or HCV PCR in blood at screening

- Completion of curative treatment for HCV within 6 months prior to screening

- HIV-2 infection

- Any vitamin D supplementation from 6 months prior to the screening 25(OH) vitamin D
test until study commencement (including multivitamins containing vitamin D and cod
liver oil)

- Any medical indication for vitamin D supplementation, eg osteoporosis, renal
impairment (estimated glomerular filtration rate < 60ml/minute), liver cirrhosis

- Chronic diarrhoea or fat malabsorption

- Body mass index (BMI >= 35)

- Current hypercalcaemia (corrected calcium greater than 2.60mM), current primary
hyperparathyroidism or any history of nephrolithiasis

- Current hyperthyroidism

- History of sarcoidosis or active tuberculosis

- Grade 3 or 4 abnormalities in screening pathology laboratory tests not already
excluded by the above criteria at the discretion of the Principal Investigator

- Hypersensitivity to vitamin D preparations

- Concurrent medication with adverse interactions with vitamin D (eg oral
glucocorticoids, phenytoin, carbamazepine, barbiturates, rifampicin, rifabutin, St
John's wort, thiazide diuretics, digoxin, ketoconazole, itraconazole, nefazodone,
isoniazid, cholestyramine, aluminium hydroxide, aripiprazole, danazol, orlistat,
perhexiline or sucralfate use) or possible such use within next 12 months

- Current interferon, immune checkpoint blocker, histone deacetylase inhibitor, oral
vitamin A or other oral vitamin A analogue (eg acitretin, isotretinoin or tretinoin,
also known as all-trans retinoic acid or ATRA) usage or possible use within next 12
months

- Current participation in another interventional HIV cure study

- Pregnancy or breast-feeding

- Participants of child-bearing potential unwilling to use at least one form of
effective contraception (with failure rate <1%, eg hormonal contraception,
intrauterine device, abstinence, tubal ligation or partner with vasectomy) from at
least 2 weeks prior to study commencement until at least 4 weeks after discontinuation
of all study medication

- Inability to consent

- Inability to speak English

- Medicare ineligibility

- Major medical or psychiatric illness or substance misuse that could in the opinion of
the investigator impair adherence to the study protocol

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
The Peter Doherty Institute for Infection and Immunity - Melbourne
Recruitment hospital [2] 0 0
The Alfred Hospital - Department of Infectious Diseases - Melbourne
Recruitment hospital [3] 0 0
Royal Melbourne Hospital - Melbourne
Recruitment hospital [4] 0 0
Melbourne Sexual Health Centre - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment postcode(s) [3] 0 0
3050 - Melbourne
Recruitment postcode(s) [4] 0 0
3053 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
University of Melbourne
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Melbourne Health
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
The Alfred
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Melbourne Sexual Health Centre
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
University of Illinois at Chicago
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Government body
Name [5] 0 0
National Institute of Allergy and Infectious Diseases (NIAID)
Address [5] 0 0
Country [5] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
HIV persists despite antiretroviral therapy (ART) and is associated with chronic
inflammation. This inflammation is thought to prevent an effective immune response against
the virus and is mediated at least in part by gut epithelial permeability and microbial
translocation. HIV accumulates preferentially within Th17 cells with time on ART; these
memory CD4+ T cells are highly susceptible to HIV infection and are concentrated within the
gut. Vitamin D promotes gut epithelial integrity in animal models and exerts
anti-inflammatory effects on the human immune system including down-modulation of Th17 cell
frequency. This study will evaluate whether high dose vitamin D is able to reduce immune
activation and Th17 cell frequency, to improve gut barrier integrity and the gut microbiome
and reduce HIV persistence in participants on long-term suppressive ART.
Trial website
https://clinicaltrials.gov/show/NCT03426592
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Sharon Lewin, FRACP PhD
Address 0 0
The Peter Doherty Institute for Infection and Immunity, University of Melbourne
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications