Breast Cancer FemaleNCT04374747
Fruit and Vegetable Intervention in Lactating Women to Reduce Breast Cancer Risk
A study testing Dietary Counseling in people with Breast Cancer Female and Inflammation, run by University of Massachusetts, Amherst at 1 site in United States.
Trial summary
Mechanistic data show that compounds in fruits and vegetables have anti-inflammatory and anti-carcinogenic properties that can reduce breast cancer risk. However, observational and interventional studies have provided mixed results, and a recent report by the American Institute for Cancer Research (AICR) concludes… Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Breast Cancer Female, Inflammation, Postpartum Weight Retention
- What is being tested?
- Dietary Counseling
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 400 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Oct 2019to 1 Apr 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Have given birth in past five weeks or are currently pregnant
- Breastfeeding baby at entry into the study
- Consuming five or fewer servings of fruits and vegetables daily at baseline
- Live within 25 miles of Amherst MA
Who cannot join
- Invasive breast cancer
- Any cancer except non-melanoma skin cancer in past five years
- History of Crohn's disease, celiac sprue, or other malabsorption syndrome, which may interfere with digesting or absorption of nutrients
- A personal history of diabetes (excluding gestational diabetes)
- Baseline BMI of <18.5
- Dietary restrictions that prevent participant from eating 8 to 10 servings of fruits and vegetables
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
University of Massachusetts Amherst
Amherst, Massachusetts, 01003
Kathleen Arcaro, PhD
About this study
Official title: Fruit and Vegetable Intervention in Lactating Women to Reduce Breast Cancer Risk: Effects on Breast Cell DNA Methylation, Breast Inflammation,and Weight
Mechanistic data show that compounds in fruits and vegetables have anti-inflammatory and anti-carcinogenic properties that can reduce breast cancer risk. However, observational and interventional studies have provided mixed results, and a recent report by the American Institute for Cancer Research (AICR) concludes that the data are insufficient but suggestive that non-starchy vegetables and foods containing carotenoids reduce risk. Measurement error, relatively low levels of carotenoid-rich fruit and vegetable intake in the study populations, emphasis on diet in later adulthood, and confounding factors likely contribute to the weak associations. Therefore, the investigators will conduct a randomized diet intervention trial in young women to assess the extent to which at least 8 to 10 daily servings of deeply pigmented and nutrient dense fruits and vegetables reduces biomarkers of breast cancer risk. The intervention is focused on breastfeeding women because: 1) pregnancy and lactation are normal early life course events; 2) the risk of pregnancy-associated breast cancer (PABC) is increased for up to 10 years postpartum; 3) a dietary intervention to reverse the detrimental molecular changes associated with puberty and pregnancy is more likely to be successful in younger than in older women;4) a diet rich in fruits and vegetables is hypothesized to reduce the inflammation during lactation/weaning and lower PABC risk; 5) postpartum lactating women may be a highly motivated population; and 6) breastmilk provides access to the breast microenvironment and breast epithelial cells to non-invasively assess the diet intervention directly in the breast. Four hundred nursing mothers will be randomly assigned to either the intervention arm, in which they are asked to increase fruit and vegetable intake to at least 8 to 10 daily servings for one year, or to a control condition in which participants receive a dietary guideline for breastfeeding mothers. Women in the intervention arm will receive counseling and boxes of fruits and vegetables for the first 20 weeks, after which they will continue to receive counseling. Changes in DNA methylation and cytokine profiles in breastmilk will be evaluated. Maternal weight and body fat distribution, and infant growth will be monitored. These results will greatly expand our knowledge of how diet alters molecular pathways in a specific organ, ultimately contributing to both breast cancer etiology and prevention.
Read the detailed description
Overview of home visits and activities completed by all participants
Visit 1 Introductory Visit (1.5 hours) 24-Hour Dietary Recalls completed during the week (1-2 hours) Occurs at 5 weeks postpartum
- Informed Consent document administered.
- Public Data Sharing Informed Consent document administered.
- Three questionnaires: New Moms Health, Physical Activity, and Breastfeeding Practices
- Maternal height, weight, and waist circumference measured.
- Instructions provided for future collection of biospecimens.
- Complete one 24-Hour Dietary Recall
- Instructions provided for two additional 24-Hour Dietary Recalls.
Visit 2 Sample Collection 1 (1.5 hours) Occurs at 6 weeks postpartum
- Provide bilateral breast milk samples and completed questionnaire.
- Provide infant stool sample and completed questionnaire.
- Two questionnaires: Infant Feeding, and Medication \& Supplement
- Infant length and weight measured.
- Maternal and infant skin carotenoids measured.
- Nutrition education provided.
- Optional collection of maternal stool sample and completed questionnaire.
Visit 3 Sample Collection 2 (1.5 hours) 24-Hour Dietary Recalls completed during the week (1-2 hours) Occurs at 16 weeks postpartum
- Provide bilateral breast milk samples and completed questionnaire.
- Provide infant stool sample and completed questionnaire.
- Three questionnaires: Physical Activity, Infant Feeding, and Medication \& Supplement
- Infant length and weight measured.
- Maternal weight and waist circumference measured.
- Maternal and infant skin carotenoids measured.
Visit 4 Sample Collection 3 (1.5 hours) 24-Hour Dietary Recalls completed during the week (1-2 hours) Occurs at 26 weeks postpartum
- Provide bilateral breast milk samples and completed questionnaire.
- Provide infant stool sample and completed questionnaire.
- Three questionnaires: Physical Activity, Infant Feeding, and Medication \& Supplement.
- Infant length and weight measured.
- Maternal weight and waist circumference measured.
- Maternal and infant skin carotenoids measured.
- Optional collection of maternal stool samples and completed questionnaire.
Visit 5 Sample Collection 4 (1.5 hours) 24-Hour Dietary Recalls completed during the week (1-2 hours) Occurs at 58 weeks postpartum
- Provide bilateral breast milk samples and completed questionnaire.
- Provide infant stool sample and completed questionnaire.
- Four questionnaires: Physical Activity, Infant Feeding, Medication and Supplement, and Breast Health
- Infant length and weight measured.
- Maternal weight and waist circumference measured.
- Maternal and infant skin carotenoids measured.
- Optional collection of maternal stool samples and completed questionnaire.
Annual Follow-up Visit (Maximum of 2) (1 hour) 24-Hour Dietary Recalls completed during the week (1-2 hours) Occurs at one-year intervals after Visit 5
- Three questionnaires: Physical Activity, Breast Health, Young Child Feeding
- Infant height and weight measured.
- Maternal weight and waist circumference measured.
- Maternal and infant skin carotenoids measured.
Monthly Inquiry (1 - 2 minutes) Occurs monthly until no longer breastfeeding
- Complete the Breast Feeding Update Questionnaire online via a survey sent through REDCap, or through a phone call.
- Conditions
- Breast Cancer Female, Inflammation, Postpartum Weight Retention, Diet, Healthy, Risk Reduction
- Being tested
- Dietary Counseling
- Medical subject headings
- Inflammation, Gestational Weight Gain, Risk Reduction Behavior
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dietary CounselingBehavioural
The counseling approach will employ strategies shown to be successful in previous and ongoing dietary modification studies including supportive and motivational interviewing techniques. Each woman in the diet intervention group will be assigned a trained nutrition coach/counselor. Counselors will focus on helping participants identify and address barriers to achieving the goal of consuming at least 8 to 10 servings of nutrient dense fruits and vegetables each day (e.g., modifying recipes and food preparation). Participants will also receive weekly boxes of fruits and vegetables .
| Study group | Role | What they receive |
|---|---|---|
| Dietary Intervention | Experimental | Intensive dietary counseling and fruit and vegetable box delivery. Receives: Behavioral: Dietary Counseling |
| Information | No intervention | Control condition of information on healthy eating during breastfeeding |
What is being measured
The primary outcome is the main question the study is designed to answer.
DNA methylation
% methylation in 300,000 CpG sites in DNA from sloughed breast epithelial cells from milk
Measured: 20 weeks
Inflammatory markers in milk
Adiponectin, CRP, IFN-y, IL1-beta, Leptin, IL-6, IL-8, TNF-alpha, b-FGF, FLT-1, PLGF, VegF-D
Measured: 20 weeks
Early weight
maternal weight
Measured: 20 weeks
Early waist circumference
maternal waist circumference
Measured: 20 weeks
One-year Weight
maternal weight
Measured: One-year
One-year Waist Circumference
maternal weight circumference
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2020
- Study start24 Oct 2019
- Primary completion1 Apr 2024 (estimated)
- Study completion1 Apr 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Breast Cancer FemaleStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Massachusetts, Amherst
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Kathleen Arcaro, PhD, Principal investigator, University of Massachusetts, AmherstLindiwe Sibeko, PhD, Principal investigator, University of Massachusetts, AmherstSusan Sturgeon, DrPH, Principal investigator, University of Massachusetts, Amherst
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04374747
- Sponsor's protocol ID
- 2019-5382
- Other IDs
- 1R01CA230478-01A1
- Status last verified
- Apr 2022
- First submitted
- 30 Apr 2020
- Last updated
- 4 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: There is no plan to make IPD available to other researchers.
Publications
Essa AR, Browne EP, Punska EC, Perkins K, Boudreau E, Wiggins H, Anderton DL, Sibeko L, Sturgeon SR, Arcaro KF. Dietary Intervention to Increase Fruit and Vegetable Consumption in Breastfeeding Women: A Pilot Randomized Trial Measuring Inflammatory Markers in Breast Milk. J Acad Nutr Diet. 2018 Dec;118(12):2287-2295. doi: 10.1016/j.jand.2018.06.015. Epub 2018 Sep 10.
PubMed 30213617Sturgeon SR, Sibeko L, Balasubramanian R, Arcaro KF. New Moms Wellness Study: the randomized controlled trial study protocol for an intervention study to increase fruit and vegetable intake and lower breast cancer risk through weekly counseling and supplemental fruit and vegetable box delivery in breastfeeding women. BMC Womens Health. 2022 Sep 24;22(1):389. doi: 10.1186/s12905-022-01967-9.
PubMed 36153518
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fruit and Vegetable Intervention in Lactating Women to Reduce Breast Cancer Risk: Effects on Breast Cell DNA Methylation, Breast Inflammation,and Weight
- ClinicalTrials.gov ID
- NCT04374747
- Acronym / sponsor ID
- 2019-5382
- Conditions
- Breast Cancer Female, Inflammation, Postpartum Weight Retention, Diet, Healthy, Risk Reduction
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- University of Massachusetts, AmherstUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 24 Oct 2019 (actual)
- Primary completion
- 1 Apr 2024 (estimated)
- Study completion
- 1 Apr 2024 (estimated)
- First posted
- 5 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Mechanistic data show that compounds in fruits and vegetables have anti-inflammatory and anti-carcinogenic properties that can reduce breast cancer risk. However, observational and interventional studies have provided mixed results, and a recent report by the American Institute for Cancer Research (AICR) concludes that the data are insufficient but suggestive that non-starchy vegetables and foods containing carotenoids reduce risk. Measurement error, relatively low levels of carotenoid-rich fruit and vegetable intake in the study populations, emphasis on diet in later adulthood, and confounding factors likely contribute to the weak associations. Therefore, the investigators will conduct a randomized diet intervention trial in young women to assess the extent to which at least 8 to 10 daily servings of deeply pigmented and nutrient dense fruits and vegetables reduces biomarkers of breast cancer risk. The intervention is focused on breastfeeding women because: 1) pregnancy and lactation are normal early life course events; 2) the risk of pregnancy-associated breast cancer (PABC) is increased for up to 10 years postpartum; 3) a dietary intervention to reverse the detrimental molecular changes associated with puberty and pregnancy is more likely to be successful in younger than in older women;4) a diet rich in fruits and vegetables is hypothesized to reduce the inflammation during lactation/weaning and lower PABC risk; 5) postpartum lactating women may be a highly motivated population; and 6) breastmilk provides access to the breast microenvironment and breast epithelial cells to non-invasively assess the diet intervention directly in the breast. Four hundred nursing mothers will be randomly assigned to either the intervention arm, in which they are asked to increase fruit and vegetable intake to at least 8 to 10 daily servings for one year, or to a control condition in which participants receive a dietary guideline for breastfeeding mothers. Women in the intervention arm will receive counseling and boxes of fruits and vegetables for the first 20 weeks, after which they will continue to receive counseling. Changes in DNA methylation and cytokine profiles in breastmilk will be evaluated. Maternal weight and body fat distribution, and infant growth will be monitored. These results will greatly expand our knowledge of how diet alters molecular pathways in a specific organ, ultimately contributing to both breast cancer etiology and prevention.
Detailed description
Overview of home visits and activities completed by all participants
Visit 1 Introductory Visit (1.5 hours) 24-Hour Dietary Recalls completed during the week (1-2 hours) Occurs at 5 weeks postpartum
- Informed Consent document administered.
- Public Data Sharing Informed Consent document administered.
- Three questionnaires: New Moms Health, Physical Activity, and Breastfeeding Practices
- Maternal height, weight, and waist circumference measured.
- Instructions provided for future collection of biospecimens.
- Complete one 24-Hour Dietary Recall
- Instructions provided for two additional 24-Hour Dietary Recalls.
Visit 2 Sample Collection 1 (1.5 hours) Occurs at 6 weeks postpartum
- Provide bilateral breast milk samples and completed questionnaire.
- Provide infant stool sample and completed questionnaire.
- Two questionnaires: Infant Feeding, and Medication \& Supplement
- Infant length and weight measured.
- Maternal and infant skin carotenoids measured.
- Nutrition education provided.
- Optional collection of maternal stool sample and completed questionnaire.
Visit 3 Sample Collection 2 (1.5 hours) 24-Hour Dietary Recalls completed during the week (1-2 hours) Occurs at 16 weeks postpartum
- Provide bilateral breast milk samples and completed questionnaire.
- Provide infant stool sample and completed questionnaire.
- Three questionnaires: Physical Activity, Infant Feeding, and Medication \& Supplement
- Infant length and weight measured.
- Maternal weight and waist circumference measured.
- Maternal and infant skin carotenoids measured.
Visit 4 Sample Collection 3 (1.5 hours) 24-Hour Dietary Recalls completed during the week (1-2 hours) Occurs at 26 weeks postpartum
- Provide bilateral breast milk samples and completed questionnaire.
- Provide infant stool sample and completed questionnaire.
- Three questionnaires: Physical Activity, Infant Feeding, and Medication \& Supplement.
- Infant length and weight measured.
- Maternal weight and waist circumference measured.
- Maternal and infant skin carotenoids measured.
- Optional collection of maternal stool samples and completed questionnaire.
Visit 5 Sample Collection 4 (1.5 hours) 24-Hour Dietary Recalls completed during the week (1-2 hours) Occurs at 58 weeks postpartum
- Provide bilateral breast milk samples and completed questionnaire.
- Provide infant stool sample and completed questionnaire.
- Four questionnaires: Physical Activity, Infant Feeding, Medication and Supplement, and Breast Health
- Infant length and weight measured.
- Maternal weight and waist circumference measured.
- Maternal and infant skin carotenoids measured.
- Optional collection of maternal stool samples and completed questionnaire.
Annual Follow-up Visit (Maximum of 2) (1 hour) 24-Hour Dietary Recalls completed during the week (1-2 hours) Occurs at one-year intervals after Visit 5
- Three questionnaires: Physical Activity, Breast Health, Young Child Feeding
- Infant height and weight measured.
- Maternal weight and waist circumference measured.
- Maternal and infant skin carotenoids measured.
Monthly Inquiry (1 - 2 minutes) Occurs monthly until no longer breastfeeding
- Complete the Breast Feeding Update Questionnaire online via a survey sent through REDCap, or through a phone call.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dietary Intervention | Experimental | Behavioral: Dietary CounselingIntensive dietary counseling and fruit and vegetable box delivery. |
| Information | No intervention | –Control condition of information on healthy eating during breastfeeding |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Have given birth in past five weeks or are currently pregnant
- Breastfeeding baby at entry into the study
- Consuming five or fewer servings of fruits and vegetables daily at baseline
- Live within 25 miles of Amherst MA
Key exclusion criteria (6 listed)
- Invasive breast cancer
- Any cancer except non-melanoma skin cancer in past five years
- History of Crohn's disease, celiac sprue, or other malabsorption syndrome, which may interfere with digesting or absorption of nutrients
- A personal history of diabetes (excluding gestational diabetes)
- Baseline BMI of <18.5
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dietary CounselingThe counseling approach will employ strategies shown to be successful in previous and ongoing dietary modification studies including supportive and motivational interviewing techniques. Each woman in the diet intervention group will be assigned a trained nutrition coach/counselor. Counselors will focus on helping participants identify and address barriers to achieving the goal of consuming at least 8 to 10 servings of nutrient dense fruits and vegetables each day (e.g., modifying recipes and food preparation). Participants will also receive weekly boxes of fruits and vegetables . | Behavioural | Dietary Intervention |
Primary outcome
DNA methylation
Time frame: 20 weeks
% methylation in 300,000 CpG sites in DNA from sloughed breast epithelial cells from milk
Inflammatory markers in milk
Time frame: 20 weeks
Adiponectin, CRP, IFN-y, IL1-beta, Leptin, IL-6, IL-8, TNF-alpha, b-FGF, FLT-1, PLGF, VegF-D
Early weight
Time frame: 20 weeks
maternal weight
Early waist circumference
Time frame: 20 weeks
maternal waist circumference
One-year Weight
Time frame: One-year
maternal weight
One-year Waist Circumference
Time frame: one year
maternal weight circumference
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2022.
- Background: PubMed 30213617Essa AR, Browne EP, Punska EC, Perkins K, Boudreau E, Wiggins H, Anderton DL, Sibeko L, Sturgeon SR, Arcaro KF. Dietary Intervention to Increase Fruit and Vegetable Consumption in Breastfeeding Women: A Pilot Randomized Trial Measuring Inflammatory Markers in Breast Milk. J Acad Nutr Diet. 2018 Dec;118(12):2287-2295. doi: 10.1016/j.jand.2018.06.015. Epub 2018 Sep 10.
- Derived from this study: PubMed 36153518Sturgeon SR, Sibeko L, Balasubramanian R, Arcaro KF. New Moms Wellness Study: the randomized controlled trial study protocol for an intervention study to increase fruit and vegetable intake and lower breast cancer risk through weekly counseling and supplemental fruit and vegetable box delivery in breastfeeding women. BMC Womens Health. 2022 Sep 24;22(1):389. doi: 10.1186/s12905-022-01967-9.
- Individual participant dataSharing planned: No. There is no plan to make IPD available to other researchers.
Related trials for Breast Cancer Female
Active, not recruitingPhase 2
Tamoxifen Citrate or Z-Endoxifen Hydrochloride in Treating Patients With Locally Advanced or Metastatic, Estrogen Receptor-Positive, HER2-Negative Breast Cancer
Recurrent Breast Carcinoma, Stage III Breast Cancer AJCC v7
Not yet recruiting
Podcast-Based Psychosocial Support for Women Newly Diagnosed With Breast Cancer
Breast Cancer
RecruitingPhase 1
A Study of LY4257496 in Participants With Cancer (OMNIRAY)
Breast Neoplasms, Colorectal Neoplasms
RecruitingObservational study
Solid Tumor Analysis for HLA Loss of Heterozygosity (LOH) and Apheresis for CAR T- Cell Manufacturing
Solid Tumor, Adult, Colorectal Cancer
Active, not recruiting
Culturally-Informed Counseling in Latinas at High Risk for Hereditary Breast or Ovarian Cancer
No Evidence of Disease, BRCA1 Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kathleen Arcaro, PhD principal investigator
University of Massachusetts, Amherst
Lindiwe Sibeko, PhD principal investigator
University of Massachusetts, Amherst
Susan Sturgeon, DrPH principal investigator
University of Massachusetts, Amherst
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Dietary Counseling in people with Breast Cancer Female and Inflammation, run by University of Massachusetts, Amherst at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 4 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Kathleen Arcaro, PhD (413-577-1823, karcaro@umass.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DNA methylation (time frame: 20 weeks). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04374747, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2022.