HR-positive Breast CancerNCT04205786

Vitamin B12 for Aromatase Inhibitors Associated Musculoskeletal Symptoms in Breast Cancer

A study testing Vitamin B12, Blood collection and Brief Pain Inventory - Short Form survey in people with HR-positive Breast Cancer, run by Case Comprehensive Cancer Center at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record

Search all trials

Trial summary

Treatment of hormone receptor (HR)-positive breast cancer with Aromatase Inhibitors (AIs) can lead to associated musculoskeletal pain and may cause patients to discontinue important treatment. This is a randomized controlled trial assessing the affect of Vitamin B12 on AI-associated joint pain and other outcomes. Read more about this study

Who is it for?: Ages 19 years and older
Conditions the study is for: HR-positive Breast Cancer
What is being tested?: Vitamin B12, Blood collection and Brief Pain Inventory - Short Form survey
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 0 participants
Where: 1 siteUnited States
Study dates: 12 Aug 2021to 1 Dec 2025
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 19 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Subjects must have histologically or cytologically confirmed estrogen receptor (ER) and/or progesterone receptor (PgR) positive invasive carcinoma of the breast (Stage I-III) with no evidence of metastatic disease (M0).
Subjects must have completed mastectomy or breast sparing surgery, and must have recovered from all side effects of the surgery. Patients should have recovered from all Grade 2 or higher side effects of chemotherapy and/or radiation therapy with the exception of alopecia and peripheral neuropathy. Concurrent bisphosphonate and trastuzumab therapies are allowed
Patients must have aromatase inhibitor (AI) associated musculoskeletal symptoms that began or increased after starting AI therapy. New musculoskeletal pain must not be due specifically to fracture or traumatic injury
Subjects must currently be taking one of the following aromatase inhibitor (AI) doses for at least 14 days prior to registration and plan to continue for at least an additional 180 days after registration:
Anastrozole (Arimidex) 1 mg daily OR
Letrozole (Femara) 2.5 mg daily OR

Show all 24Show fewer

Exemestane (Aromasin) 25 mg daily
Patients must be post-menopausal, as defined by at least one of the following:
--≥ 12 months since their last menstrual period OR
Prior bilateral oophorectomy OR
Previous hysterectomy with one or both ovaries left in place (or previous hysterectomy in which documentation of bilateral oophorectomy is unavailable) AND (unless ≥ 60 years of age) FSH values consistent with the institutional normal values for the post-menopausal state.
Performance status: Patients must have ECOG performance status of 0-2 as assessed by MD or RN
Patients must have no known allergy or hypersensitivity to vitamin B12
Must have completed the Brief Pain Inventory Short Form (BPI-SF) within 7 days of enrollment (after signing consent, but prior to starting treatment) and have an "average pain" score of at least 24.
Patients must not have any contraindicated concurrent illnesses including:
History of alcohol or other substance abuse or dependence within 365 days prior to enrollment.
Chronic liver disease.
End stage renal disease.
Patients who are receiving treatment with narcotics, tramadol, gabapentin, and/or pregabalin must have been taking a stable dose for at least 30 days prior to registration.
Patients must be able to complete study questionnaires in English.
Patients who are currently taking vitamin B12 or a multivitamin containing vitamin B12 will be able to participate in the study after having stopped taking the vitamin B12 or the multivitamin containing the B12 for two weeks before day 1 of treatment.
Patients must be willing to submit blood samples for laboratory testing [to test for Serum Vitamin B12, CRP, homocysteine level, complete blood count (CBC), potassium, and MMA]. Baseline samples must be obtained prior to beginning protocol treatment.
All patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.
Subjects must have the ability to understand and the willingness to sign a written informed consent document.

Who cannot join

Subjects receiving any other investigational agents.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to vitamin B12 or other agents used in this study.
Subjects with uncontrolled intercurrent illness including, but not limited to chronic liver disease, end stage renal disease, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Trial locations and contacts

1 site in 1 country.

United States1 site

Cleveland Clinic Taussig Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, 44195

Other trials in United States

About this study

Official title: A Randomized Study of Oral Vitamin B12 for the Treatment of Aromatase Inhibitors (AI)-Associated Musculoskeletal Symptoms (AIMSS) in Women With Early Stage Breast Cancer

Treatment of hormone receptor (HR)-positive breast cancer with Aromatase Inhibitors (AIs) can lead to associated musculoskeletal pain and may cause patients to discontinue important treatment.

This is a randomized controlled trial assessing the affect of Vitamin B12 on AI-associated joint pain and other outcomes. Participants will be randomly assigned 1:1 to treatment or control arm.

The primary objective of this study is:

-To assess whether daily oral Vitamin B12 decreases average joint pain in women with AI-Associated Musculoskeletal Symptoms

Secondary objectives include:

To investigate whether daily vitamin B12 improves functional quality of life
To explore the impact of treatment on serum inflammatory cytokine levels (C- reactive protein) between baseline and various points in treatment.

Read the detailed description

According to the American Cancer Society, there were more than 250,000 new breast cancer cases in 2017. Incidence of breast cancer increases with age, with more than 75% of patients being postmenopausal at the time of diagnosis. In addition, hormone receptors (HR) are over expressed in the majority of breast cancer tumors in postmenopausal women.

Two classes of anti-endocrine therapies are used for treatment of HR-positive breast cancer: tamoxifen and the AIs, which can only be used to treat postmenopausal women because they are ineffective in women with functional ovaries. Joint pain is a significant AI-associated toxicity, affecting as many as 50% of patients. No factors associated with breast cancer treatment (such as chemotherapy) or co-morbid conditions (such as diabetes or body mass index) have been clearly shown to be predictive of the development of joint pain. The cause of AI-associated musculoskeletal symptoms remains elusive but some think it is associated with the direct effects of estrogen deprivation on bone, neurohormonal changes which result in change in pain sensitivity, and immune system changes that alter the circulating or local inflammatory cytokine concentrations.

Some studies report more than 20% of patients are no longer taking their AI chemotherapy regimen because of AI-associated joint pain. As many as 40,000 women are affected by this toxicity in the United States annually and up to 20,000 women discontinue AI therapy because of intolerable joint pain and muscle aches. The current treatment for AI associated musculoskeletal symptoms is limited to oral pain medications and exercise, but, neither intervention has optimal effects, and the long term use of oral pain medication is problematic. Improvement in the treatment of AI associated musculoskeletal symptoms is needed to improve compliance with therapy, and thereby lead to improved breast cancer outcomes and survivorship.

The study team conducted a pilot study (Campbell et al. Breast J, 2018) which suggested that vitamin B12 reduces pain and improves quality of life for participants taking aromatase inhibitors (AIs) who experienced AI-related musculoskeletal symptoms. This study aims to confirm these results in a phase III randomized prospective trial. If confirmed, Vitamin B12 would become a safe and cost-effective option for the treatment of AI-related musculoskeletal symptoms, leading to improved cancer outcomes and survivorship.

Conditions: HR-positive Breast Cancer
Being tested: Vitamin B12, Blood collection, Brief Pain Inventory - Short Form survey, FACT-ES Trial Outcome Index (Version 4), Questionnaire to Assess Adherence to Aromatase Inhibitors

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Vitamin B12Dietary supplement
Vitamin B12, orally, 2500 mcg, daily, for 90 days
Blood collectionOther
Blood collection for laboratory testing will occur within 10 days of signing the consent form, on day 45 +/- 10 days, and on day 90 +/- 10 days. It will include:
1. Serum B12 levels
2. CRP
3. Homocysteine level
4. MMA
Brief Pain Inventory - Short Form surveyOther
Brief Pain Inventory - Short Form survey
FACT-ES Trial Outcome Index (Version 4)Other
FACT-ES Trial Outcome Index (Version 4)
Questionnaire to Assess Adherence to Aromatase InhibitorsOther
Questionnaire to Assess Adherence to Aromatase Inhibitors
Demographics QuestionnaireOther
Demographics Questionnaire

Study groups in NCT04205786
Study group	Role	What they receive
Control - Standard of Care	Active comparator	Day 0: * Baseline questionnaires: FACT-ES, BPI-SF, Assessment of AI Adherence, Demographics, CRF, and Supplemental Agents Reporting Form * Blood collection * Continue Usual Care Day 45: * Repeat of baseline questionnaires with addition of vitamin B12 supplements form and investigational agent accountability record * Blood collection * Continue Usual Care Day 90: -Repeat of day 45 Receives: Other: Blood collection; Other: Brief Pain Inventory - Short Form survey; Other: FACT-ES Trial Outcome Index (Version 4); Other: Questionnaire to Assess Adherence to Aromatase Inhibitors; Other: Demographics Questionnaire
Study Medication Group (B12)	Experimental	Day 0: * Baseline questionnaires: FACT-ES, BPI-SF, Assessment of AI Adherence, Demographics, CRF, and Supplemental Agents Reporting Form * Blood collection * Oral intake of Vitamin B12 Daily in the morning Day 45 * Repeat of baseline questionnaires with addition of investigational agent accountability record * Blood collection * Oral intake of Vitamin B12 Daily in the morning Day 90: -Repeat of day 45 without additional study drug intake. Receives: Dietary Supplement: Vitamin B12; Other: Blood collection; Other: Brief Pain Inventory - Short Form survey; Other: FACT-ES Trial Outcome Index (Version 4); Other: Questionnaire to Assess Adherence to Aromatase Inhibitors; Other: Demographics Questionnaire

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in average joint pain according to the Brief Pain Inventory - Short Form (BPI- SF)
Change in average joint pain according to the Brief Pain Inventory - Short Form (BPI- SF) average pain score. This item has a scale of 0 to 10 with 0 indicating "No pain" and 10 indicating "Pain as bad as you can imagine"
Measured: At baseline, day 45 (+/- 10 days), and at day 90 (+/- 10 days)

Secondary outcomes (2)

Change in worst joint pain according to the BPI-SF
Change in worst joint pain according to the BPI-SF worst (maximum) pain score. This item has a scale of 0 to 10 with 0 indicating "No pain" and 10 indicating "Pain as bad as you can imagine".
Measured: At day 90 (+/- 10 days)
Quality of life (QOL) as measured by Functional Assessment of Cancer Therapy-Endocrine Scale (FACT-ES)
Quality of life (QOL) as measured by Functional Assessment of Cancer Therapy-Endocrine Scale (FACT-ES) a 5-point scale (0-4) with 0 being better, 4 being worse.
Measured: At baseline, day 45 (+/- 10 days), and at day 90 (+/- 10 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

12 Aug 20211 Dec 2025

First posted19 Dec 2019
Study start12 Aug 2021
Primary completion1 Dec 2024 (estimated)
Study completion1 Dec 2025 (estimated)

Why it stopped: Logistics requirements, research cancelled

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for HR-positive Breast CancerStudies of the same condition, open and under way.
More trials run by Case Comprehensive Cancer CenterThe sponsor's other registered studies.
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: Supportive care
Allocation: Randomised
Intervention model: Parallel groups
Model description: The study is a randomized controlled trial. Participants will be randomly assigned 1:1 to treatment or control arm.
Masking: None (open label)
Enrolment: 0 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04205786
Sponsor's protocol ID: CASE5119
Status last verified: Aug 2024
First submitted: 18 Dec 2019
Last updated: 21 Aug 2024
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: Manuscripts, presentations, abstracts

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingPhase 1/2
Study of Oral MRT-2359 in Selected Cancer Patients
NSCLC, SCLC
RecruitingObservational study
Patient Relevant Outcomes Improvement Program in High Risk Hormone Receptor Positive (HR+) Breast Cancer
HR+/HER2- Early Breast Cancer
RecruitingPhase 3
Adding an Immunotherapy Drug, MEDI4736 (Durvalumab), to the Usual Chemotherapy Treatment (Paclitaxel, Cyclophosphamide, and Doxorubicin) for Stage II-III Breast Cancer
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8
Not yet recruitingPhase 1
A Study to Evaluate the Effects of GDC-4198 in Combination With Letrozole, Fulvestrant, or Giredestrant in Participants With Locally Advanced or Metastatic Hormone Receptor-Positive, HER2-Negatve Breast Cancer
Advanced or Metastatic Breast Cancer
RecruitingPhase 3
Phase 3 Study of RLY-2608 + Fulvestrant vs Capivasertib + Fulvestrant as Treatment for Locally Advanced or Metastatic PIK3CA-mutant HR+/HER2- Breast Cancer
PIK3CA Mutation, HER2- Negative Breast Cancer

All HR-positive Breast Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 21 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized Study of Oral Vitamin B12 for the Treatment of Aromatase Inhibitors (AI)-Associated Musculoskeletal Symptoms (AIMSS) in Women With Early Stage Breast Cancer
ClinicalTrials.gov ID: NCT04205786
Acronym / sponsor ID: CASE5119
Conditions: HR-positive Breast Cancer
Study type: Interventional
Recruitment status: WithdrawnReason stopped: Logistics requirements, research cancelled
Enrolment: 0 participants (actual)
Lead sponsor: Case Comprehensive Cancer CenterUniversity, hospital or other
Study start: 12 Aug 2021 (actual)
Primary completion: 1 Dec 2024 (estimated)
Study completion: 1 Dec 2025 (estimated)
First posted: 19 Dec 2019 (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.

Treatment of hormone receptor (HR)-positive breast cancer with Aromatase Inhibitors (AIs) can lead to associated musculoskeletal pain and may cause patients to discontinue important treatment.

This is a randomized controlled trial assessing the affect of Vitamin B12 on AI-associated joint pain and other outcomes. Participants will be randomly assigned 1:1 to treatment or control arm.

The primary objective of this study is:

-To assess whether daily oral Vitamin B12 decreases average joint pain in women with AI-Associated Musculoskeletal Symptoms

Secondary objectives include:

To investigate whether daily vitamin B12 improves functional quality of life
To explore the impact of treatment on serum inflammatory cytokine levels (C- reactive protein) between baseline and various points in treatment.

Detailed description

Study design

Primary purpose: Supportive care
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2
Model description: The study is a randomized controlled trial. Participants will be randomly assigned 1:1 to treatment or control arm.

Arm	Type	Receives
Control - Standard of Care	Active comparator	Other: Blood collection, Other: Brief Pain Inventory - Short Form survey, Other: FACT-ES Trial Outcome Index (Version 4), Other: Questionnaire to Assess Adherence to Aromatase Inhibitors, Other: Demographics QuestionnaireDay 0: * Baseline questionnaires: FACT-ES, BPI-SF, Assessment of AI Adherence, Demographics, CRF, and Supplemental Agents Reporting Form * Blood collection * Continue Usual Care Day 45: * Repeat of baseline questionnaires with addition of vitamin B12 supplements form and investigational agent accountability record * Blood collection * Continue Usual Care Day 90: -Repeat of day 45
Study Medication Group (B12)	Experimental	Dietary Supplement: Vitamin B12, Other: Blood collection, Other: Brief Pain Inventory - Short Form survey, Other: FACT-ES Trial Outcome Index (Version 4), Other: Questionnaire to Assess Adherence to Aromatase Inhibitors, Other: Demographics QuestionnaireDay 0: * Baseline questionnaires: FACT-ES, BPI-SF, Assessment of AI Adherence, Demographics, CRF, and Supplemental Agents Reporting Form * Blood collection * Oral intake of Vitamin B12 Daily in the morning Day 45 * Repeat of baseline questionnaires with addition of investigational agent accountability record * Blood collection * Oral intake of Vitamin B12 Daily in the morning Day 90: -Repeat of day 45 without additional study drug intake.

Who may qualify

Ages: 19 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (24 listed)

Subjects must have histologically or cytologically confirmed estrogen receptor (ER) and/or progesterone receptor (PgR) positive invasive carcinoma of the breast (Stage I-III) with no evidence of metastatic disease (M0).
Subjects must have completed mastectomy or breast sparing surgery, and must have recovered from all side effects of the surgery. Patients should have recovered from all Grade 2 or higher side effects of chemotherapy and/or radiation therapy with the exception of alopecia and peripheral neuropathy. Concurrent bisphosphonate and trastuzumab therapies are allowed
Patients must have aromatase inhibitor (AI) associated musculoskeletal symptoms that began or increased after starting AI therapy. New musculoskeletal pain must not be due specifically to fracture or traumatic injury
Subjects must currently be taking one of the following aromatase inhibitor (AI) doses for at least 14 days prior to registration and plan to continue for at least an additional 180 days after registration:
Patients must be post-menopausal, as defined by at least one of the following:

Key exclusion criteria (3 listed)

Subjects receiving any other investigational agents.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to vitamin B12 or other agents used in this study.
Subjects with uncontrolled intercurrent illness including, but not limited to chronic liver disease, end stage renal disease, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

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
Vitamin B12Vitamin B12, orally, 2500 mcg, daily, for 90 days	Dietary supplement	Study Medication Group (B12)
Blood collectionBlood collection for laboratory testing will occur within 10 days of signing the consent form, on day 45 +/- 10 days, and on day 90 +/- 10 days. It will include: 1. Serum B12 levels 2. CRP 3. Homocysteine level 4. MMA	Other	Control - Standard of Care, Study Medication Group (B12)
Brief Pain Inventory - Short Form surveyBrief Pain Inventory - Short Form survey	Other	Control - Standard of Care, Study Medication Group (B12)
FACT-ES Trial Outcome Index (Version 4)FACT-ES Trial Outcome Index (Version 4)	Other	Control - Standard of Care, Study Medication Group (B12)
Questionnaire to Assess Adherence to Aromatase InhibitorsQuestionnaire to Assess Adherence to Aromatase Inhibitors	Other	Control - Standard of Care, Study Medication Group (B12)
Demographics QuestionnaireDemographics Questionnaire	Other	Control - Standard of Care, Study Medication Group (B12)

Primary outcome

Change in average joint pain according to the Brief Pain Inventory - Short Form (BPI- SF)
Time frame: At baseline, day 45 (+/- 10 days), and at day 90 (+/- 10 days)
Change in average joint pain according to the Brief Pain Inventory - Short Form (BPI- SF) average pain score. This item has a scale of 0 to 10 with 0 indicating "No pain" and 10 indicating "Pain as bad as you can imagine"

2 secondary outcomes

Change in worst joint pain according to the BPI-SF
Time frame: At day 90 (+/- 10 days)
Quality of life (QOL) as measured by Functional Assessment of Cancer Therapy-Endocrine Scale (FACT-ES)
Time frame: At baseline, day 45 (+/- 10 days), and at day 90 (+/- 10 days)

Results and safety

The study was withdrawn before enrolling participants, so there are no results.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2024.
Individual participant dataSharing planned: Yes. Manuscripts, presentations, abstracts

Related trials for HR-positive Breast Cancer

Active, not recruitingPhase 1/2
Study of Oral MRT-2359 in Selected Cancer Patients
NSCLC, SCLC
RecruitingObservational study
Patient Relevant Outcomes Improvement Program in High Risk Hormone Receptor Positive (HR+) Breast Cancer
HR+/HER2- Early Breast Cancer
RecruitingPhase 3
Adding an Immunotherapy Drug, MEDI4736 (Durvalumab), to the Usual Chemotherapy Treatment (Paclitaxel, Cyclophosphamide, and Doxorubicin) for Stage II-III Breast Cancer
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage III Breast Cancer AJCC v8
Not yet recruitingPhase 1
A Study to Evaluate the Effects of GDC-4198 in Combination With Letrozole, Fulvestrant, or Giredestrant in Participants With Locally Advanced or Metastatic Hormone Receptor-Positive, HER2-Negatve Breast Cancer
Advanced or Metastatic Breast Cancer
RecruitingPhase 3
Phase 3 Study of RLY-2608 + Fulvestrant vs Capivasertib + Fulvestrant as Treatment for Locally Advanced or Metastatic PIK3CA-mutant HR+/HER2- Breast Cancer
PIK3CA Mutation, HER2- Negative Breast Cancer

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.

Zeina Nahleh, MD principal investigator

Cleveland Clinic Taussig Cancer Center, Case Comprehensive Cancer Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 24 inclusion and 3 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: withdrawn, as of the sponsor's last update on 21 Aug 2024. 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?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in average joint pain according to the Brief Pain Inventory - Short Form (BPI- SF) (time frame: At baseline, day 45 (+/- 10 days), and at day 90 (+/- 10 days)). 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 NCT04205786.

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 21 Aug 2024.