Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001699853
Ethics application status
Approved
Date submitted
24/09/2021
Date registered
10/12/2021
Date last updated
10/12/2021
Date data sharing statement initially provided
10/12/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
The ENHANCE study. Can a daily supplement improve egg quality?
The effects of NR (Nicotinamide riboside) supplementation on the egg quality of women of advanced age undergoing IVF: a randomised placebo-controlled double-blind proof of concept clinical trial
Scientific title
The ENHANCE study. Can a daily supplement improve egg quality?
The effects of NR (Nicotinamide riboside) supplementation on the egg quality of women of advanced age undergoing IVF: a randomised placebo-controlled double-blind proof of concept clinical trial
Secondary ID [1] 304110 0
Nil known
Universal Trial Number (UTN)
U1111-1269-7929
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Infertility 323713 0
Poor ovarian reserve 323715 0
Condition category
Condition code
Reproductive Health and Childbirth 321248 321248 0 0
Fertility including in vitro fertilisation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients who are eligible to join the study will be randomised into three groups. Women will be using NR - Nicotinamide Riboside (TRU NIAGEN - TGA listed ARTG number 328365), as oral capsules, at the dosage of 250mg, 1000mg or placebo once a day for six weeks before the trigger (36 hours before the egg collection) in an IVF treatment cycle. As a strategy to monitor adherence to the intervention, the research nurse will call each participant after 14 days of medication use to check for compliance. In addition, after the participant’s first clinic visit, (approximately 28 days since commencing the study medication), the participant will be seen by research staff to count their study medication to check for compliance.
Intervention code [1] 321781 0
Treatment: Drugs
Comparator / control treatment
Control: Placebo capsules (microcrystalline cellulose)
Control group
Placebo

Outcomes
Primary outcome [1] 329032 0
Number of day 5 blastocysts per patient, assessed by study fertility specialist
Timepoint [1] 329032 0
Seven days post conclusion of intervention
Secondary outcome [1] 401229 0
Number of oocytes retrieved, assessed by study fertility specialist
Timepoint [1] 401229 0
Two days post conclusion of intervention
Secondary outcome [2] 401230 0
Final estradiol level - serum assay
Timepoint [2] 401230 0
Six weeks post commencement of intervention
Secondary outcome [3] 401231 0
Fertilisation rates, calculated as the percentage of oocytes that turn into two pronuclei after a fertilisation procedure. This outcome will be assessed by study fertility specialist.
Timepoint [3] 401231 0
Three days post conclusion of intervention
Secondary outcome [4] 401232 0
Number of embryos surviving to D3, defined by the number of embryos that survives in culture medium for at least 3 days, which will be assessed by the study fertility specialist.
Timepoint [4] 401232 0
Five days post conclusion of intervention
Secondary outcome [5] 401233 0
Clinical pregnancy rates - gestational sac with fetal heart beat diagnosed by transvaginal ultrasound at 6 weeks of pregnancy
Timepoint [5] 401233 0
Ten weeks post conclusion of intervention
Secondary outcome [6] 401234 0
Pregnancy outcomes - we will record APGAR scores as surrogate for health of the child. Data will be collected from medical records.
Timepoint [6] 401234 0
Forty four to forty six weeks post conclusion of intervention. This is a one-time assessment (at the day of birth).
Secondary outcome [7] 401235 0
NR safety - analysed through a composite of side effects (which will be registered by the research team firstly within 48 hours of commencement of medication to check for any adverse events, then after 14 days, then on each visit during ovarian stimulation that will occur every 2-3 days) and pregnancy outcomes. Data will be collected from the audit of study records.
Timepoint [7] 401235 0
From day one of intervention until birth if the patient conceives as a result of the treatment.
Secondary outcome [8] 401236 0
Bioavailability of NAD in blood - Serum assay
Timepoint [8] 401236 0
Six weeks post commencement of intervention and two days post conclusion of intervention, respectively
Secondary outcome [9] 401237 0
Oocyte quality - analysed as a composite at a molecular level (samples of cumulus cells and follicular fluid will be obtained) and through non-invasive imaging of oocytes using polarised light microscopy and deep radiomic imaging
Timepoint [9] 401237 0
Two days post conclusion of intervention
Secondary outcome [10] 402391 0
Pregnancy outcomes - we will record birth weight at day of birth. Data will be collected from medical records.
Timepoint [10] 402391 0
Forty four to forty six weeks post conclusion of intervention. This is a one-time assessment (at the day of birth).
Secondary outcome [11] 402392 0
Bioavailability of NAD in follicular fluid - Serum assay
Timepoint [11] 402392 0
Six weeks post commencement of intervention and two days post conclusion of intervention, respectively

Eligibility
Key inclusion criteria
Female patients undergoing IVF aged greater than or equal to 36 years at the time of randomisation
Minimum age
36 Years
Maximum age
42 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Consumption of herbal medicine or additional supplements except for preconception multivitamins

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 (RedCap)
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
Participants are randomly allocated to receive either 250mg or 1000mg of NR or placebo
Phase
Phase 2 / Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Descriptive statistics will be presented by mean, SD, maximum and minimum for continuous variables, and the number of cases (n) and rate (%) for dichotomous variables. To explore the association between the number of retrieved oocytes and the number of blastocysts, univariable and multivariable regression analyses will be used. This study is a proof-of-concept trial to evaluate whether there is any evidence of the benefit of NR compared with the placebo.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
15/12/2021
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 308491 0
University
Name [1] 308491 0
University of New South Wales - UNSW
Country [1] 308491 0
Australia
Primary sponsor type
University
Name
University of New South Wales - UNSW
Address
DVC Research Office, UNSW, Sydney, NSW, 2052, Australia
Country
Australia
Secondary sponsor category [1] 310763 0
None
Name [1] 310763 0
Address [1] 310763 0
Country [1] 310763 0
Other collaborator category [1] 281991 0
Commercial sector/Industry
Name [1] 281991 0
CERP - ChromaDex External Research Program
Address [1] 281991 0
10005 Muirlands Blvd., Suite G - Irvine, CA 92618 USA
Country [1] 281991 0
United States of America

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308448 0
SESLHD - HREC / Research Ethics and Governance Office
Ethics committee address [1] 308448 0
District Executive Unit, Level4
The Sutherland Hospital & Community Health Service
Cnr The Kingsway & Kareena Road
Caringbah - NSW 2229
Ethics committee country [1] 308448 0
Australia
Date submitted for ethics approval [1] 308448 0
Approval date [1] 308448 0
20/09/2021
Ethics approval number [1] 308448 0

Summary
Brief summary
The Enhance study is a randomised placebo-controlled double-blind proof of concept clinical trial to analyse whether using a daily supplement can improve egg quality. Women between the age of 36 and 42 requiring IVF trying to conceive will be randomised for the use of NR at the dosage of 250mg, 1000mg, or placebo, once a day for six weeks before the trigger (36 hours before the egg collection) in an IVF cycle. A primary outcome will be analysing the number of day 5 blastocysts and secondary outcomes: number of oocytes retrieved, final estradiol level, fertilisation rates, number of embryos surviving to D3, pregnancy rates and outcomes, and NR safety. We will also be evaluating the bioavailability of NAD in blood and follicular fluid and oocyte quality.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 110734 0
Prof William Ledger
Address 110734 0
School of Women's & Children's Health, University of New South Wales Level 1, Royal Hospital for Women, Barker Street (Locked Bag 2000), RANDWICK, NSW 2031
Country 110734 0
Australia
Phone 110734 0
+61 02 9382 6515
Fax 110734 0
Email 110734 0
[email protected]
Contact person for public queries
Name 110735 0
Mrs Galina Lazareva
Address 110735 0
Level 1, Royal Hospital for Women Barker Street, RANDWICK NSW 2031
Country 110735 0
Australia
Phone 110735 0
+61 02 9382 6515
Fax 110735 0
Email 110735 0
[email protected]
Contact person for scientific queries
Name 110736 0
Prof Robert Gilchrist
Address 110736 0
School of Women's & Children's Health, University of New South Wales Level 1, Royal Hospital for Women, Barker Street (Locked Bag 2000), RANDWICK, NSW 2031
Country 110736 0
Australia
Phone 110736 0
+61 02 9065 2241
Fax 110736 0
Email 110736 0
[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


What supporting documents are/will be available?




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.