Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000372785
Ethics application status
Approved
Date submitted
16/02/2022
Date registered
3/03/2022
Date last updated
3/03/2022
Date data sharing statement initially provided
3/03/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Replenishing a vital molecule in stiff heart failure patients and examining effect on heart stiffness, blood pressure, and exercise tolerance
Scientific title
Replenishing cardiac levels of oxidized nicotinamide adenine dinucleotide with precursor nicotinamide riboside in patients with heart failure with preserved ejection fraction, and determination of the effect on cardiac diastolic function, exercise tolerance, blood pressure, and glucose tolerance
Secondary ID [1] 306445 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) 325283 0
Condition category
Condition code
Cardiovascular 322684 322684 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Determining if oral supplementation with nicotinamide riboside (precursor of NAD+) for 3 months can improve left ventricular diastolic function.
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: drug tablet return, verbal confirmation
Intervention code [1] 322876 0
Treatment: Drugs
Comparator / control treatment
The placebo will also be given twice per day for 3 months. Placebo is provided by the same commercial supplier (Chromadex) and consists of the same capsule shape, colour, texture but with nicotinamide riboside (NR) replaced by Microcystalline Cellulose.
Control group
Placebo

Outcomes
Primary outcome [1] 330480 0
Left ventricular diastolic function assessed by echocardiography using transmitral doppler and strain assessment
Timepoint [1] 330480 0
Three months after commencing treatment
Secondary outcome [1] 406389 0
Blood pressure assessed using a digital sphygmomanometer
Timepoint [1] 406389 0
Three months after commencing treatment.
Secondary outcome [2] 406723 0
Exercise tolerance assessed using the standard Bruce Protocol exercise stress test
Timepoint [2] 406723 0
Three months after commencing treatment
Secondary outcome [3] 406724 0
Glucose tolerance assessed using the oral glucose tolerance test (OGTT) per the NSW Chemical Pathology laboratory protocols
Timepoint [3] 406724 0
Three months after commencing treatment

Eligibility
Key inclusion criteria
1. All members of the specialist HFpEF clinic at RPAH who consent. In order to be a member of the HFpEF clinic, patients have met the following criteria at the time of clinic admission:
a. Recent hospital admission (within the previous 12 months) with heart failure
b. Left ventricular ejection fraction greater than or equal to 45% on echocardiogram within the previous 6 months
2. Concomitant diseases: all patients who consent, regardless of concomitant disease. Except for end-stage renal disease (CKD greater than or equal to stage 4), liver failure (hepatic encephalopathy with impaired synthetic function as determined by INR greater than or equal to 1.5 in the absence of anticoagulant therapy) or malignant cancer.
3. Willingness to provide informed consent and willingness to participate.
4. Agreement of the treating cardiologist.
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 greater than or equal to stage 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 that 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
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 4
Type of endpoint/s
Efficacy
Statistical methods / analysis
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.

The primary outcome is left ventricular global longitudinal strain. This, and the secondary outcome data, will be assessed after examination of data distribution. 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. Statistical significance will be reached when there is a p-value <0.05.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
5/04/2022
Actual
Date of last participant enrolment
Anticipated
8/04/2025
Actual
Date of last data collection
Anticipated
9/07/2025
Actual
Sample size
Target
400
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 21746 0
Royal Prince Alfred Hospital - Camperdown
Recruitment postcode(s) [1] 36800 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 310793 0
Government body
Name [1] 310793 0
NSW Government
Country [1] 310793 0
Australia
Funding source category [2] 310797 0
Charities/Societies/Foundations
Name [2] 310797 0
Heart Foundation
Country [2] 310797 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] 312080 0
None
Name [1] 312080 0
Address [1] 312080 0
Country [1] 312080 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310365 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 310365 0
Research Ethics and Governance Office (REGO), Royal Prince Alfred Hospital, Missenden Road, CAMPERDOWN NSW 2050
Ethics committee country [1] 310365 0
Australia
Date submitted for ethics approval [1] 310365 0
Approval date [1] 310365 0
03/02/2022
Ethics approval number [1] 310365 0

Summary
Brief summary
We recently discovered a deficiency of oxidized nicotinamide adenine dinucleotide in the hearts of patients with stiff heart failure. We have shown that replenishing heart levels of this molecule in a mouse model of stiff heart failure can completely rescue this disease.
Now, we will deliver the same precursor of this molecule, as used in mice, to human patients with this disease, for three months.
At the end of the three months, we will determine if they have had any benefits in heart stiffness, exercise tolerance, blood pressure, and glucose tolerance.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 117398 0
Prof John O'Sullivan
Address 117398 0
Room 3E71, Charles Perkins Centre, The University of Sydney, Camperdown, NSW 2006
Country 117398 0
Australia
Phone 117398 0
+61 2 8627 5600
Fax 117398 0
Email 117398 0
John.O'[email protected]
Contact person for public queries
Name 117399 0
Prof John O'Sullivan
Address 117399 0
Room 3E71, Charles Perkins Centre, The University of Sydney, Camperdown, NSW 2006
Country 117399 0
Australia
Phone 117399 0
+61 2 8627 5600
Fax 117399 0
Email 117399 0
John.O'[email protected]
Contact person for scientific queries
Name 117400 0
Prof John O'Sullivan
Address 117400 0
Room 3E71, Charles Perkins Centre, The University of Sydney, Camperdown, NSW 2006
Country 117400 0
Australia
Phone 117400 0
+61 2 8627 5600
Fax 117400 0
Email 117400 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
Restriction under therapeutic product supplier agreement


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.