Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000340730
Ethics application status
Approved
Date submitted
16/02/2022
Date registered
24/02/2022
Date last updated
24/02/2022
Date data sharing statement initially provided
24/02/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Testing the ability of oral nicotinamide riboside to replenish heart tissue levels of oxidized nicotinamide adenine dinucleotide using heart biopsies taken at the time of surgery.
Scientific title
Determining Feasibility of Human Myocardial NAD+ Replenishment using Oral Nicotinamide Riboside Supplementation in Adults with Diastolic Dysfunction – The CardioNAD Study
Secondary ID [1] 306432 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Heart failure with preserved ejection fraction (HFpEF) 325277 0
Condition category
Condition code
Cardiovascular 322676 322676 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Determining if oral supplementation of the NAD+ precursor nicotinamide riboside (NR) at a dose of 1g twice per day is sufficient to replenish left ventricular myocardial NAD+ levels and to improve mitochondrial respiration.
Supplement Details:
Generic name: Nicotinamide riboside (NR). Supplier: Chromadex. Dose administered: 1g twice/day of NR. Duration of administration: one month. Mode of administration: oral capsule.
Compliance strategies: drug tablet return, verbal confirmation
Intervention code [1] 322870 0
Treatment: Drugs
Comparator / control treatment
Placebo is provided by Chromadex as part of a commercial agreement; placebo is carefully matched to appear indistinguishable from NR, and consists of pre-capsulated Microcrystalline Cellulose with the same capsule size and colour, meeting the criteria for double-blinding.
Control group
Placebo

Outcomes
Primary outcome [1] 330470 0
NAD+ levels in left ventricular myocardial biopsy retrieved at the time of cardiothoracic surgery, using our established NAD+ assay on liquid chromatography mass spectrometry
Timepoint [1] 330470 0
One month after commencing treatment
Secondary outcome [1] 406345 0
NAMPT mRNA levels in left ventricular myocardium tissue biopsy, retrieved at the time of cardiothoracic surgery, measured using qRT-PCR
Timepoint [1] 406345 0
one month after commencing treatment

Eligibility
Key inclusion criteria
1. All participants who have equal to or greater than Grade 2 diastolic dysfunction
2. Male and female
3. Adults equal to or greater than 18 years of age
4. Concomitant diseases: all patients eligible regardless of concomitant disease. Except for end-stage renal disease (CKD equal to or greater than 4) or end-stage liver disease or malignant cancer.
5. Willingness to provide informed consent and willingness to participate.
6. Agreement of the treating cardiothoracic surgeon.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Participants with end-stage kidney (CKD equal to or greater than 4) or liver failure (hepatic encephalopathy with impaired synthetic function as determined by INR equal to or greater than 1.5 in the absence of anticoagulant therapy).
2. Participants with a history of a psychological illness or other conditions which may interfere with their ability to understand the study requirements.
3. Patients already taking NAD+ precursors including niacin, nicotinamide, or nicotinamide riboside

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)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 4
Type of endpoint/s
Bio-availability
Statistical methods / analysis
Sample size estimation:
Based on preliminary data showing a 2.7 fold increase in myocardial NAD+ levels with NR supplementation, with SD of 0.4, we estimate that n equal to 20 patients per group will be required to determine a significant different in NAD+ levels between groups with 80% power at alpha equal to 0.05.

Statistical Analysis Plan
Metabolite peaks will be integrated using MultiQuant v.3.0.3, blinded to group. Metabolite concentration/mg wet tissue will be determined using external standard curves and corrected for recovery using controls spiked with the same standards used for the curves. Normality of distribution will be tested using Shapiro-Wilks. In cases of non-normality, logarithmic transformation will be used. Pairwise comparison will employ statistical tests that don’t assume normal distribution, e.g. Welch’s t-test or Mann-Whitney rank sum test. qPCR NAMPT data will be expressed relative to expression in normal donor tissue from the Sydney Heart Bank using the 2SDC(q) method , with the geometric mean of Cq values for ACTB, B2M, and GAPDH used as internal control. Optimal stability of housekeeping genes will be determined using RefFinder. C(q) values will be log-transformed before statistical analyses, with the same pairwise comparison considerations as above.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
5/04/2022
Actual
Date of last participant enrolment
Anticipated
2/04/2024
Actual
Date of last data collection
Anticipated
4/06/2024
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 21742 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 36796 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 310779 0
Government body
Name [1] 310779 0
NSW Government
Country [1] 310779 0
Australia
Funding source category [2] 310787 0
Charities/Societies/Foundations
Name [2] 310787 0
The Heart Foundation
Country [2] 310787 0
Australia
Primary sponsor type
Government body
Name
Sydney Local Health District
Address
Level 11, KGV Building
Missenden Road
CAMPERDOWN NSW 2050
Country
Australia
Secondary sponsor category [1] 312081 0
None
Name [1] 312081 0
Address [1] 312081 0
Country [1] 312081 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310354 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 310354 0
Ethics committee country [1] 310354 0
Australia
Date submitted for ethics approval [1] 310354 0
Approval date [1] 310354 0
03/02/2022
Ethics approval number [1] 310354 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 117354 0
Prof John O'Sullivan
Address 117354 0
Room 3E71, Charles Perkins Centre, The University of Sydney, Camperdown, NSW 2006
Country 117354 0
Australia
Phone 117354 0
+61 2 8627 5600
Fax 117354 0
Email 117354 0
John.O'[email protected]
Contact person for public queries
Name 117355 0
John O'Sullivan
Address 117355 0
Room 3E71, Charles Perkins Centre, The University of Sydney, Camperdown, NSW 2006
Country 117355 0
Australia
Phone 117355 0
+61 2 8627 5600
Fax 117355 0
Email 117355 0
John.O'[email protected]
Contact person for scientific queries
Name 117356 0
John O'Sullivan
Address 117356 0
Room 3E71, Charles Perkins Centre, The University of Sydney, Camperdown, NSW 2006
Country 117356 0
Australia
Phone 117356 0
+61 2 8627 5600
Fax 117356 0
Email 117356 0
John.O'[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Limitation conferred by commercial agreement with supplier of nicotinamide riboside


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.