Ignite Creation Date:
2024-07-17 @ 11:00 AM
Last Modification Date:
2024-10-26 @ 3:34 PM
Study NCT ID:
NCT06497270
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-07-11
First Post:
2024-06-26
Brief Title:
A 3D Bioprinted Hormone-producing Model for BRCA Mutated Patients After Risk Reducing Surgery the DISC-OVARY Trial
Sponsor:
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Organization:
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Study Overview
Official Title:
A 3D Bioprinted Hormone-producing Model for BRCA Mutated Patients After Risk Reducing Surgery the DISC-OVARY Trial
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
DISC-OVARY
Brief Summary:
Selecting theca and granulosa cells from removed ovaries of BRCA12mut patients undergoing Risk-reducing salpingo-oophorectomy RRSO and developing a 3D bioprinted hormone-producing bioprosthetic model If efficacy and tolerability are confirmed in vivo this bioprosthetic model might be used to replace hormones production in BRCA mutated patients undergoing prophylactic surgery
Detailed Description:
Background and Rationale Women carrying germline BReast CAncer gene BRCA 12 mutations have an increased lifetime risk of breast and ovarian cancers 72 and 44 for BRCA1 and 69 and 17 for BRCA2 respectively Risk-reducing salpingo-oophorectomy RRSO by the age of 40 postponable to age of 45 for BRCA2mut is the standard of care in ovarian cancer risk reduction about 80 Although potentially lifesaving RRSO may negatively affect quality of life and impair long-term health cardiovascular disease osteoporosis and impairment of immune response
To overcome these side effects hormone replacement therapy HRT is crucial but remains a major concern especially due to its negative effects potential breast cancer risk thromboembolic events and overall due to the long-term safety lack of data Synthetic and animal-derived hormones seem to be associated with breast cancer risk Although breast cancer risk is lower for bioidentical hormones ie estriol data continue to be discordant Several evidence still sustain estriols impact on breast cancer especially for lobular histotype OR 20 95 CI 13-32 and endometrial disease endometrial cancer OR 30 95 CI 20-44 and endometrial atypical hyperplasia OR 83 95 CI 40-174 respectively Furthermore estriols efficacy on cardiovascular disease and osteoporosis is still unclear when compared to other estrogen compounds Side effects of estriol therapy may include breast tenderness nausea bloating mood changes headache and vaginal bleeding or spotting Moreover all the HRTs administration routes oral transdermal and vaginal need dailyfrequent assumption thus compliance of the patients is essential and adherence to long-term therapy in developed countries is reported around 50 with a high risk of forgetfulness or discontinuation Each route also has specific disadvantages ie the risk of thromboembolism in the oral one Finally HRT may influence other hormones production it increases T4 dosage requirements of women being treated for primary hypothyroidism as well as alter the pituitary-thyroid axis in euthyroid women While for cortisol level findings are still inconsistent hormone exogenous intake does not permit to follow the daily hormonal fluctuation Aging and hypoestrogenism in postmenopausal women determine immune system changes which may play a crucial role in the development of postmenopausal diseases diabetes or atherosclerosis and may be negatively influenced by HRT Preliminary data of a recent MITO group survey revealed that only 70 of gynecologists recommend HRT after RRSO due to oncological safety concerns and low womens requests more than 70 of cases were oral prescriptions while only 24 preferred local administration
In conclusion for some women the concern of menopause risks act as a deterrent for a lifesaving procedure RRSO In this scenario it is fundamental to provide a new strategy for BRCA mutated patients in order to reduce menopausal drawbacks without exposing participants to a higher breast cancer risk reproducing the physiological hormonal rhythm without compliance issue The 3D bioprinted hormone-producing model from patients own autologous cells could meet this need
HYPOTHESIS The investigators hypothesize to select theca and granulosa cells from removed ovaries of BRCA12mut patients undergoing RRSO avoiding the epithelial ones at risk of developing cancer and use those cells to develop a 3D bioprinted hormone-producing bioprosthetic model in order to replace patients own production
AIMS Primary endpoint Restore normal estrogen and progesterone serum level in participants undergoing RRSO by the 3D bioprinted hormone-producing models implant
EXPERIMENTAL DESIGN No study has previously investigated the feasibility of 3D bioprinted hormone-producing model hence this configures as a pilot study which as such does not need any formal sample size calculation
The proposed research project aims to select theca and granulosa cells from patients removed ovaries combine them with different ratios of extracted mesenchymal cells print them onto the prosthetic model scaffolds and assess the hormone production
IMPACT ON CANCER The results of the pilot project will provide a 3D bioprinted model able to produce estrogens and progesterone in vitro If functionality is confirmed in vivo the model might be used in BRCA mutated patients allowing them to avoid surgery induced menopauses side effects Specifically a 3D bioprinted hormone-producing bioprosthetic model would provide patients with a viable alternative to surgery-induced menopause and traditional HRT
To overcome these side effects hormone replacement therapy HRT is crucial but remains a major concern especially due to its negative effects potential breast cancer risk thromboembolic events and overall due to the long-term safety lack of data Synthetic and animal-derived hormones seem to be associated with breast cancer risk Although breast cancer risk is lower for bioidentical hormones ie estriol data continue to be discordant Several evidence still sustain estriols impact on breast cancer especially for lobular histotype OR 20 95 CI 13-32 and endometrial disease endometrial cancer OR 30 95 CI 20-44 and endometrial atypical hyperplasia OR 83 95 CI 40-174 respectively Furthermore estriols efficacy on cardiovascular disease and osteoporosis is still unclear when compared to other estrogen compounds Side effects of estriol therapy may include breast tenderness nausea bloating mood changes headache and vaginal bleeding or spotting Moreover all the HRTs administration routes oral transdermal and vaginal need dailyfrequent assumption thus compliance of the patients is essential and adherence to long-term therapy in developed countries is reported around 50 with a high risk of forgetfulness or discontinuation Each route also has specific disadvantages ie the risk of thromboembolism in the oral one Finally HRT may influence other hormones production it increases T4 dosage requirements of women being treated for primary hypothyroidism as well as alter the pituitary-thyroid axis in euthyroid women While for cortisol level findings are still inconsistent hormone exogenous intake does not permit to follow the daily hormonal fluctuation Aging and hypoestrogenism in postmenopausal women determine immune system changes which may play a crucial role in the development of postmenopausal diseases diabetes or atherosclerosis and may be negatively influenced by HRT Preliminary data of a recent MITO group survey revealed that only 70 of gynecologists recommend HRT after RRSO due to oncological safety concerns and low womens requests more than 70 of cases were oral prescriptions while only 24 preferred local administration
In conclusion for some women the concern of menopause risks act as a deterrent for a lifesaving procedure RRSO In this scenario it is fundamental to provide a new strategy for BRCA mutated patients in order to reduce menopausal drawbacks without exposing participants to a higher breast cancer risk reproducing the physiological hormonal rhythm without compliance issue The 3D bioprinted hormone-producing model from patients own autologous cells could meet this need
HYPOTHESIS The investigators hypothesize to select theca and granulosa cells from removed ovaries of BRCA12mut patients undergoing RRSO avoiding the epithelial ones at risk of developing cancer and use those cells to develop a 3D bioprinted hormone-producing bioprosthetic model in order to replace patients own production
AIMS Primary endpoint Restore normal estrogen and progesterone serum level in participants undergoing RRSO by the 3D bioprinted hormone-producing models implant
EXPERIMENTAL DESIGN No study has previously investigated the feasibility of 3D bioprinted hormone-producing model hence this configures as a pilot study which as such does not need any formal sample size calculation
The proposed research project aims to select theca and granulosa cells from patients removed ovaries combine them with different ratios of extracted mesenchymal cells print them onto the prosthetic model scaffolds and assess the hormone production
IMPACT ON CANCER The results of the pilot project will provide a 3D bioprinted model able to produce estrogens and progesterone in vitro If functionality is confirmed in vivo the model might be used in BRCA mutated patients allowing them to avoid surgery induced menopauses side effects Specifically a 3D bioprinted hormone-producing bioprosthetic model would provide patients with a viable alternative to surgery-induced menopause and traditional HRT
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None