Vulvovaginal AtrophyPhase 4GRACENCT05562518
GRACE-trial: a Randomized Active-controlled Trial for vulvovaGinal atRophy in breAst Cancer Patients on Endocrine Therapy.
A Phase 4 study testing Estrogen, dehydroepiandrosterone and Estrogen + probiotics in people with Vulvovaginal Atrophy and Breast Cancer, run by University Hospital, Ghent at 1 site in Belgium.
Trial summary
In this prospective active-controlled randomized trial the investigators will assess for the first time ever the different local treatments of vulvovaginal atrophy in breast cancer patients on endocrine therapy. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Vulvovaginal Atrophy, Breast Cancer
- What is being tested?
- Estrogen, dehydroepiandrosterone and Estrogen + probiotics
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteBelgium
- Study dates
- 21 Mar 2022to 2 Mar 2026
- Phase
- Phase 4
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- breast cancer patient
- current endocrine therapy (AI or SERM)
- postmenopausal status, defined by:
- 12 months amenorrhoea or
- 6 months amenorrhoe and FSH level of >40 mIU/mL or
- >6 weeks after bilateral oophorectomy or
- induced postmenopause (ovarian function suppression using GnRH-analogue)
- presence of one or more symptoms of vulvovaginal atrophy (dyspareunia, dryness, irritation)
Who cannot join
- a history of vulvar or vaginal surgery (Inclusion is possible after hysterectomy. For these subjects no microbiome sampling will be performed. Microbiome analysis is not performed for these subjects.)
- current other vulvar or vaginal disease
- recent use of antibiotics/antifungals/corticosteroids (less than 1 month)
- current use of vaginal hormonal treatment or vaginal moisturizer: inclusion is possible after a washout period of 4 weeks
Trial locations and contacts
1 site in 1 country.
About this study
In this prospective active-controlled randomized trial the investigators will assess for the first time ever the different local treatments of vulvovaginal atrophy in breast cancer patients on endocrine therapy. These patients are currently inadequately treated based on ignorance of possible treatment modalities and stigmatization of vulvovaginal atrophy.
Read the detailed description
In this prospective active-controlled randomized trial the investigators will assess for the first time ever the different local treatments of vulvovaginal atrophy in breast cancer patients on endocrine therapy. These patients are currently inadequately treated based on ignorance of possible treatment modalities and stigmatization of vulvovaginal atrophy.
While current knowledge on comparative data of the local treatments of vulvovaginal atrophy is based on retrospective data or one-to-one comparisons, we will prospectively evaluate all different local treatments based on patient-reported outcome measurements. This new data is mandatory for increasing the awareness of physicians of the treatment possibilities of vulvovaginal atrophy in breast cancer patients. Together with the use of different communication channels towards patients, this combination will substantially contribute to the increase of quality-of-life of breast cancer patients with vulvovaginal atrophy.
The primary objectives in this trial are two-fold. The first primary objective addresses the efficacy of the different implemented treatment strategies based on patient-reported outcome measurements (PROMs). These PROMs will be implemented prior to treatment and after initiation of the implemented treatments (estrogen, DHEA, probiotics or moisturizer). By implementing repeated PROM assessment, longitudinal evaluation of symptom alterations due to the treatment can be objectified.
The second primary objective is the safety evaluation of the implemented treatments. This evaluation will be achieved by measuring the sex hormone concentrations systemically with repeated longitudinal measurements.
In this study, the investigators will measure sex hormone concentrations through high-sensitive assessments based on LC-MS/MS. Considering the ALARA (as low a reasonably achievable) principle in radiation safety, we could extrapolate this ALARA principle to the safety of the local hormonal treatment of vulvovaginal atrophy in breast cancer patients, where potential differences in increase of sex hormone concentrations between the different treatment modalities could be objectified. Despite previous literature that could not show increased recurrence of breast cancer, this finding will play an import role in the decision-making of treatment of vulvovaginal atrophy in breast cancer patients. As mentioned earlier, a direct comparison of these sex hormone concentrations for the different treatment modalities is currently lacking.
As translational secondary objective, the investigators aim to investigate the microbial alterations when using local treatment for vulvovaginal atrophy. Identification of these alterations will contribute in understanding the pathophysiology of vulvovaginal atrophy and may unravel changes caused by the local treatment and may create opportunities in the future for additive treatment or new therapeutic strategies to ameliorate the quality-of-life of breast cancer patients with vulvovaginal atrophy.
- Conditions
- Vulvovaginal Atrophy, Breast Cancer
- Being tested
- Estrogen, dehydroepiandrosterone, Estrogen + probiotics, Moisturizer
- Keywords
- breast cancer, vulvovaginal atrophy, endocrine therapy
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EstrogenDrug
1 vaginal ovule daily for three consecutive weeks, followed by 1 vaginal ovule 2 times per week
dehydroepiandrosteroneDrug
1 vaginal ovule daily
Estrogen + probioticsDrug
1 vaginal ovule daily for 12 consecutive days, followed by 1 vaginal ovule 2 times per week
MoisturizerDrug
1 vaginal ovule daily for 14 consecutive days, followed by 1 vaginal ovule every three days
| Study group | Role | What they receive |
|---|---|---|
| Estrogen | Active comparator | locally administered estrogen (oestriol) Receives: Drug: Estrogen |
| Dehydroepiandrosterone | Active comparator | locally administered dehydroepiandrosterone (DHEA) Receives: Drug: dehydroepiandrosterone |
| Estrogen + probiotics | Active comparator | locally administered estrogen (oestriol) + probiotics Receives: Drug: Estrogen + probiotics |
| Moisturizer | Active comparator | locally administered hyaluronic acid Receives: Drug: Moisturizer |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in symptoms and quality of life after implementation of treatment in a time frame of 12 weeks using the EQ5D-questionnaire.
Efficacy of the implemented treatments will be assessed based on patient-reported outcome measurements (PROM) that describe symptoms and quality-of-life.
The first primary outcome will be based on assessment using the EQ5D-questionnaire.
This endpoint will be assessed at three time points: at start, after 6 weeks, and at the end (after 12 weeks). The change in these PROMs will be evaluated over the predefined timeframe of 12 weeks.
The EQ5D-questionnaire includes a scale describing the general health of the participant at the predefined times, using a metric scale from 0 to 100 (0 being the worst health and 100 being the best health).
Measured: 12 weeks
Change in symptoms and quality of life after implementation of treatment in a time frame of 12 weeks using the FACT-ES questionnaire.
Efficacy of the implemented treatments will be assessed based on patient-reported outcome measurements (PROM) that describe symptoms and quality-of-life.
The second primary outcome will be based on assessment using the FACT-ES-questionnaire.
This endpoint will be assessed at three time points: at start, after 6 weeks, and at the end (after 12 weeks). The change in these PROMs will be evaluated over the predefined timeframe of 12 weeks.
The FACT-ES consists of question with answer possibilities from 0 to 4 (with the higher the score, the better the quality of life).
Measured: 12 weeks
Change in sex steroid hormone concentrations in a time frame of 12 weeks.
The change in concentration of sex steroid hormone concentration as a surrogate for safety be be evaluated by measuring the sex hormone concentrations systemically with repeated longitudinal measurements. This endpoint will be assessed at three time points: at start, after 6 weeks, and at the end (after 12 weeks). The following sex steroid hormone concentrations will be assessed: estrone, estradiol, DHEA-S, DHEA, testosterone, and dihydrotestosterone.
Measured: 12 weeks
Secondary outcomes (1)
Identification of vaginal microbial alterations after implementation of treatment.
The vaginal microbiome will be determined at start and after 12 weeks. Bacterial DNA will be extracted and the microbiota will be identified using cpn60 sequencing. The change in microbial profiles between the two timepoints will be assessed.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2022
- Study start21 Mar 2022
- Primary completion2 Mar 2026
- Study completion2 Mar 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Vulvovaginal AtrophyStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Ghent
- Sponsor type
- University, hospital or other
- Collaborators
- University Ghent
- Responsible party
- Sponsor
- Investigators
- Hans Verstraelen, MD, PhD, Principal investigator, University Hospital, Ghent
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05562518
- Sponsor's protocol ID
- BC-09638
- Acronym
- GRACE
- Status last verified
- Aug 2026
- First submitted
- 7 Feb 2022
- Last updated
- 13 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- GRACE-trial: a Randomized Active-controlled Trial for vulvovaGinal atRophy in breAst Cancer Patients on Endocrine Therapy.
- ClinicalTrials.gov ID
- NCT05562518
- Acronym / sponsor ID
- GRACE / BC-09638
- Conditions
- Vulvovaginal Atrophy, Breast Cancer
- Keywords
- breast cancer, vulvovaginal atrophy, endocrine therapy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- University Hospital, GhentUniversity, hospital or other
- Collaborators
- University Ghent
- Study start
- 21 Mar 2022 (actual)
- Primary completion
- 2 Mar 2026 (actual)
- Study completion
- 2 Mar 2026 (actual)
- First posted
- 30 Sep 2022 (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.
In this prospective active-controlled randomized trial the investigators will assess for the first time ever the different local treatments of vulvovaginal atrophy in breast cancer patients on endocrine therapy. These patients are currently inadequately treated based on ignorance of possible treatment modalities and stigmatization of vulvovaginal atrophy.
Detailed description
In this prospective active-controlled randomized trial the investigators will assess for the first time ever the different local treatments of vulvovaginal atrophy in breast cancer patients on endocrine therapy. These patients are currently inadequately treated based on ignorance of possible treatment modalities and stigmatization of vulvovaginal atrophy.
While current knowledge on comparative data of the local treatments of vulvovaginal atrophy is based on retrospective data or one-to-one comparisons, we will prospectively evaluate all different local treatments based on patient-reported outcome measurements. This new data is mandatory for increasing the awareness of physicians of the treatment possibilities of vulvovaginal atrophy in breast cancer patients. Together with the use of different communication channels towards patients, this combination will substantially contribute to the increase of quality-of-life of breast cancer patients with vulvovaginal atrophy.
The primary objectives in this trial are two-fold. The first primary objective addresses the efficacy of the different implemented treatment strategies based on patient-reported outcome measurements (PROMs). These PROMs will be implemented prior to treatment and after initiation of the implemented treatments (estrogen, DHEA, probiotics or moisturizer). By implementing repeated PROM assessment, longitudinal evaluation of symptom alterations due to the treatment can be objectified.
The second primary objective is the safety evaluation of the implemented treatments. This evaluation will be achieved by measuring the sex hormone concentrations systemically with repeated longitudinal measurements.
In this study, the investigators will measure sex hormone concentrations through high-sensitive assessments based on LC-MS/MS. Considering the ALARA (as low a reasonably achievable) principle in radiation safety, we could extrapolate this ALARA principle to the safety of the local hormonal treatment of vulvovaginal atrophy in breast cancer patients, where potential differences in increase of sex hormone concentrations between the different treatment modalities could be objectified. Despite previous literature that could not show increased recurrence of breast cancer, this finding will play an import role in the decision-making of treatment of vulvovaginal atrophy in breast cancer patients. As mentioned earlier, a direct comparison of these sex hormone concentrations for the different treatment modalities is currently lacking.
As translational secondary objective, the investigators aim to investigate the microbial alterations when using local treatment for vulvovaginal atrophy. Identification of these alterations will contribute in understanding the pathophysiology of vulvovaginal atrophy and may unravel changes caused by the local treatment and may create opportunities in the future for additive treatment or new therapeutic strategies to ameliorate the quality-of-life of breast cancer patients with vulvovaginal atrophy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Estrogen | Active comparator | Drug: Estrogenlocally administered estrogen (oestriol) |
| Dehydroepiandrosterone | Active comparator | Drug: dehydroepiandrosteronelocally administered dehydroepiandrosterone (DHEA) |
| Estrogen + probiotics | Active comparator | Drug: Estrogen + probioticslocally administered estrogen (oestriol) + probiotics |
| Moisturizer | Active comparator | Drug: Moisturizerlocally administered hyaluronic acid |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- breast cancer patient
- current endocrine therapy (AI or SERM)
- postmenopausal status, defined by:
- >6 weeks after bilateral oophorectomy or
- presence of one or more symptoms of vulvovaginal atrophy (dyspareunia, dryness, irritation)
Key exclusion criteria (4 listed)
- a history of vulvar or vaginal surgery (Inclusion is possible after hysterectomy. For these subjects no microbiome sampling will be performed. Microbiome analysis is not performed for these subjects.)
- current other vulvar or vaginal disease
- recent use of antibiotics/antifungals/corticosteroids (less than 1 month)
- current use of vaginal hormonal treatment or vaginal moisturizer: inclusion is possible after a washout period of 4 weeks
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 |
|---|---|---|
| Estrogen1 vaginal ovule daily for three consecutive weeks, followed by 1 vaginal ovule 2 times per week | Drug | Estrogen |
| dehydroepiandrosterone1 vaginal ovule daily | Drug | Dehydroepiandrosterone |
| Estrogen + probiotics1 vaginal ovule daily for 12 consecutive days, followed by 1 vaginal ovule 2 times per week | Drug | Estrogen + probiotics |
| Moisturizer1 vaginal ovule daily for 14 consecutive days, followed by 1 vaginal ovule every three days | Drug | Moisturizer |
Primary outcome
Change in symptoms and quality of life after implementation of treatment in a time frame of 12 weeks using the EQ5D-questionnaire.
Time frame: 12 weeks
Efficacy of the implemented treatments will be assessed based on patient-reported outcome measurements (PROM) that describe symptoms and quality-of-life. The first primary outcome will be based on assessment using the EQ5D-questionnaire. This endpoint will be assessed at three time points: at start, after 6 weeks, and at the end (after 12 weeks). The change in these PROMs will be evaluated over the predefined timeframe of 12 weeks. The EQ5D-questionnaire includes a scale describing the general health of the participant at the predefined times, using a metric scale from 0 to 100 (0 being the worst health and 100 being the best health).
Change in symptoms and quality of life after implementation of treatment in a time frame of 12 weeks using the FACT-ES questionnaire.
Time frame: 12 weeks
Efficacy of the implemented treatments will be assessed based on patient-reported outcome measurements (PROM) that describe symptoms and quality-of-life. The second primary outcome will be based on assessment using the FACT-ES-questionnaire. This endpoint will be assessed at three time points: at start, after 6 weeks, and at the end (after 12 weeks). The change in these PROMs will be evaluated over the predefined timeframe of 12 weeks. The FACT-ES consists of question with answer possibilities from 0 to 4 (with the higher the score, the better the quality of life).
Change in sex steroid hormone concentrations in a time frame of 12 weeks.
Time frame: 12 weeks
The change in concentration of sex steroid hormone concentration as a surrogate for safety be be evaluated by measuring the sex hormone concentrations systemically with repeated longitudinal measurements. This endpoint will be assessed at three time points: at start, after 6 weeks, and at the end (after 12 weeks). The following sex steroid hormone concentrations will be assessed: estrone, estradiol, DHEA-S, DHEA, testosterone, and dihydrotestosterone.
1 secondary outcome
Identification of vaginal microbial alterations after implementation of treatment.
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2026.
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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.
Hans Verstraelen, MD, PhD principal investigator
University Hospital, Ghent
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Estrogen, dehydroepiandrosterone and Estrogen + probiotics in people with Vulvovaginal Atrophy and Breast Cancer, run by University Hospital, Ghent at 1 site in Belgium.
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 8 inclusion and 4 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: finished, as of the sponsor's last update on 13 Aug 2026. 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 Belgium. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 symptoms and quality of life after implementation of treatment in a time frame of 12 weeks using the EQ5D-questionnaire. (time frame: 12 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Aug 2026.