Ignite Creation Date:
2024-05-06 @ 3:36 PM
Last Modification Date:
2024-10-26 @ 1:52 PM
Study NCT ID:
NCT04685148
Status:
RECRUITING
Last Update Posted:
2021-09-23
First Post:
2020-12-16
Brief Title:
Maternal Mental Health Trial
Sponsor:
Vibe G Frøkjær MD PhD
Organization:
Rigshospitalet Denmark
Study Overview
Official Title:
Short Time Oestrogen as a Candidate Strategy to Prevent Postpartum Depression in a High-risk Group a Randomised Placebo-controlled Trial
Status:
RECRUITING
Status Verified Date:
2021-09
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:
MAMA
Brief Summary:
Perinatal depression affects 10-15 of women postpartum and has a recurrence rate of 40 Women who develop perinatal depression might be particularly susceptible to the rapid and large changes in sex steroid hormones particularly estradiol across pregnancy to postpartum This trial aims 1 to evaluate the preventive effect of transdermal estradiol treatment in the immediate postpartum on depressive episodes in a subgroup of women at high-risk for perinatal depression and 2 to determine if a set of biomarker gene transcripts can identify this subgroup and thus form the basis for future personalised prevention or treatment
The MAMA Trial is a double-blind 11 randomised placebo-controlled trial The trial involves maternity wards at three university hospitals in the Capital Region of Denmark Women who are singleton pregnant in the third trimester with a prior history of perinatal depression are eligible to participate Participants will be randomised to either estradiol patches 200 μg per day or placebo patches for three weeks starting immediately postpartum
The primary statistical analysis will be performed based on the intention-to-treat principle A sample size of 220 will provide the trial with 80 power alpha 005 beta 02 to detect a reduction in postpartum depression of 50 and to tolerate a drop-out of around 20
The MAMA Trial is a double-blind 11 randomised placebo-controlled trial The trial involves maternity wards at three university hospitals in the Capital Region of Denmark Women who are singleton pregnant in the third trimester with a prior history of perinatal depression are eligible to participate Participants will be randomised to either estradiol patches 200 μg per day or placebo patches for three weeks starting immediately postpartum
The primary statistical analysis will be performed based on the intention-to-treat principle A sample size of 220 will provide the trial with 80 power alpha 005 beta 02 to detect a reduction in postpartum depression of 50 and to tolerate a drop-out of around 20
Detailed Description:
Major depressive disorder affects twice as many women as men Women are at increased risk for depression in life phases where endogenous sex steroid hormone milieu changes such as in puberty during late pregnancy to postpartum and across menopausal transition This includes a subtype of MDD perinatal depression PND that affects 10-15 of mothers postpartum and has a recurrence rate of 40 in subsequent pregnancies PND is a disabling disorder that affects the entire family including development and future health of the infant
The underlying risk and resilience mechanisms in MDD are far from clear consequently current treatment strategies are suboptimal Women who develop PND might be particularly sensitive to the rapid and large changes in sex steroid hormone milieu seen in the transition from high levels of sex steroid hormones in particular estradiol in pregnancy to low levels in the hormone withdrawal phase postpartum Thus PND is most likely has a distinct pathophysiology which may provide a unique opportunity for protecting mental health by targeted short-term prevention in the immediate postpartum period
Intriguingly recent human data has provided direct evidence for sex hormone manipulation to provoke subclinical depressive symptoms in about 12 of healthy volunteers The phenomenon was linked to changes in estradiol which were induced by the pharmacological manipulation with a Gonadotrophin Releasing Hormone agonist Estradiol affects critical domains and key brain regions known to be dysfunctional in women with major depressive disorder Estradiol sensitivity predisposes to PND which can be demonstrated at the level of gene transcription in clinical cohorts and is also directly supported by recent research results Such peripheral markers of estradiol sensitivity may prove useful in identifying individuals at excess risk for PND also in their first pregnancy and thus may help direct preventive efforts for the women who can benefit the most
Transdermal estradiol emerges as a promising preventive treatment option for the postpartum onset of PND supported by epidemiological preclinical and clinical research robust and rapid response to estradiol in some pilot postpartum depression PPD trials with few side effects and minimal breastmilk passage to the infant Further transdermal estradiol appears to be effective in preventing clinically significant depressive symptoms among perimenopausal women which is another group of women in hormonal transition phase
Previously a double-blind randomized controlled trial RCT showed effect of treatment with transdermal estradiol on manifest PND A recent pilot RCT with transdermal estradiol as a candidate treatment for postpartum depression failed to achieve its primary outcome but notably did reduce depressive symptoms postpartum compared to placebo
Rather than treating manifest depressive episodes postpartum the investigators here propose a different approach to target and potentially prevent early risk mechanisms in the first three weeks postpartum and to direct this preventive strategy towards women in high risk This immediate and early postpartum timing corresponds to the peak risk period and covers the peak of hormonal decline postpartum
This trial aims 1 to evaluate the preventive effect of transdermal estradiol treatment in the immediate postpartum on depressive episodes in a subgroup of women at high risk for Perinatal Depression with postpartum onset and 2 to determine if a set of biomarker gene transcripts can identify this subgroup and thus form the basis for future personalized prevention or treatment
Methods The Maternal Mental Health MAMA Trial is designed as a double-blind 11 randomized placebo-controlled superiority trial setting involving maternity wards at three university hospitals in the Capital Region of Denmark
Women who are singleton pregnant in third trimester with a prior history of perinatal depression onset before six months postpartum and aged 18 to 45 years are eligible to participate
The women will be assessed for eligibility by the midwife or obstetrician when attending antenatal care at the outpatient clinic Eligible participants who verbally consent to receive more information about the trial will subsequently be contacted by telephone Written informed consent is obtained before inclusion in the MAMA Trial
The randomisation will be conducted by the capital region pharmacy Trial participants clinical care providers research assistants investigators outcome assessors and data analysists will all be blinded to allocation
The investigators calculated that a sample of 288 complete cases would provide the trial with 80 power at a two-sided alpha level of 005 to detect a reduction in postpartum depression of 50 Thus with a study number of 2110 the design is considered solid and can tolerate 22 dropouts
The primary statistical analysis will be performed on basis of the intention-to-treat principle The investigators will compare data on the primary outcome for the two groups for the superiority of estradiol over placebo with Pearsons chi-squared test
Secondary outcomes with a continuous distribution will be compared between groups with respect to the mean Students t-test if the distribution is unimodal and symmetric or to the median if the distribution is unimodal but asymmetric or otherwise to the ranks of the observations Mann-Whitney test A test on the difference in proportions will be used for binary secondary outcomes and a Pearsons chi-squared test will be used for categorical data
As a sensitivity analysis we will use an instrumental variable approach to estimate causal treatment effect using randomisation as an instrument
Ethical considerations The short-term administration of estradiol transdermally is not expected to pose unacceptable or intolerable side-effects disrupt breastfeeding or pass to the infant in any dosages that may pose a risk to the infant Should un-expected side effects for mother or infant occur or be suspected the treatment will be disrupted immediately When removing the patch serum concentrations of estradiol return to baseline levels within 24 hours Participants who develop levels of mental distress or depressive symptoms that approach clinical thresholds will be referred to relevant and timely psychiatric care by a trained clinician All potentially sensitive personal data will be anonymized The trial will adhere closely to the Helsinki declaration
Prospect There is a pressing need to develop a preventive strategy to depressive episodes during pregnancy and childbirth that is targeted cheap short-term and easy to implement Such work holds promise to positively affect womens mental health their families and importantly if successful may also improve long-term outcomes of the infants physical and mental health
The underlying risk and resilience mechanisms in MDD are far from clear consequently current treatment strategies are suboptimal Women who develop PND might be particularly sensitive to the rapid and large changes in sex steroid hormone milieu seen in the transition from high levels of sex steroid hormones in particular estradiol in pregnancy to low levels in the hormone withdrawal phase postpartum Thus PND is most likely has a distinct pathophysiology which may provide a unique opportunity for protecting mental health by targeted short-term prevention in the immediate postpartum period
Intriguingly recent human data has provided direct evidence for sex hormone manipulation to provoke subclinical depressive symptoms in about 12 of healthy volunteers The phenomenon was linked to changes in estradiol which were induced by the pharmacological manipulation with a Gonadotrophin Releasing Hormone agonist Estradiol affects critical domains and key brain regions known to be dysfunctional in women with major depressive disorder Estradiol sensitivity predisposes to PND which can be demonstrated at the level of gene transcription in clinical cohorts and is also directly supported by recent research results Such peripheral markers of estradiol sensitivity may prove useful in identifying individuals at excess risk for PND also in their first pregnancy and thus may help direct preventive efforts for the women who can benefit the most
Transdermal estradiol emerges as a promising preventive treatment option for the postpartum onset of PND supported by epidemiological preclinical and clinical research robust and rapid response to estradiol in some pilot postpartum depression PPD trials with few side effects and minimal breastmilk passage to the infant Further transdermal estradiol appears to be effective in preventing clinically significant depressive symptoms among perimenopausal women which is another group of women in hormonal transition phase
Previously a double-blind randomized controlled trial RCT showed effect of treatment with transdermal estradiol on manifest PND A recent pilot RCT with transdermal estradiol as a candidate treatment for postpartum depression failed to achieve its primary outcome but notably did reduce depressive symptoms postpartum compared to placebo
Rather than treating manifest depressive episodes postpartum the investigators here propose a different approach to target and potentially prevent early risk mechanisms in the first three weeks postpartum and to direct this preventive strategy towards women in high risk This immediate and early postpartum timing corresponds to the peak risk period and covers the peak of hormonal decline postpartum
This trial aims 1 to evaluate the preventive effect of transdermal estradiol treatment in the immediate postpartum on depressive episodes in a subgroup of women at high risk for Perinatal Depression with postpartum onset and 2 to determine if a set of biomarker gene transcripts can identify this subgroup and thus form the basis for future personalized prevention or treatment
Methods The Maternal Mental Health MAMA Trial is designed as a double-blind 11 randomized placebo-controlled superiority trial setting involving maternity wards at three university hospitals in the Capital Region of Denmark
Women who are singleton pregnant in third trimester with a prior history of perinatal depression onset before six months postpartum and aged 18 to 45 years are eligible to participate
The women will be assessed for eligibility by the midwife or obstetrician when attending antenatal care at the outpatient clinic Eligible participants who verbally consent to receive more information about the trial will subsequently be contacted by telephone Written informed consent is obtained before inclusion in the MAMA Trial
The randomisation will be conducted by the capital region pharmacy Trial participants clinical care providers research assistants investigators outcome assessors and data analysists will all be blinded to allocation
The investigators calculated that a sample of 288 complete cases would provide the trial with 80 power at a two-sided alpha level of 005 to detect a reduction in postpartum depression of 50 Thus with a study number of 2110 the design is considered solid and can tolerate 22 dropouts
The primary statistical analysis will be performed on basis of the intention-to-treat principle The investigators will compare data on the primary outcome for the two groups for the superiority of estradiol over placebo with Pearsons chi-squared test
Secondary outcomes with a continuous distribution will be compared between groups with respect to the mean Students t-test if the distribution is unimodal and symmetric or to the median if the distribution is unimodal but asymmetric or otherwise to the ranks of the observations Mann-Whitney test A test on the difference in proportions will be used for binary secondary outcomes and a Pearsons chi-squared test will be used for categorical data
As a sensitivity analysis we will use an instrumental variable approach to estimate causal treatment effect using randomisation as an instrument
Ethical considerations The short-term administration of estradiol transdermally is not expected to pose unacceptable or intolerable side-effects disrupt breastfeeding or pass to the infant in any dosages that may pose a risk to the infant Should un-expected side effects for mother or infant occur or be suspected the treatment will be disrupted immediately When removing the patch serum concentrations of estradiol return to baseline levels within 24 hours Participants who develop levels of mental distress or depressive symptoms that approach clinical thresholds will be referred to relevant and timely psychiatric care by a trained clinician All potentially sensitive personal data will be anonymized The trial will adhere closely to the Helsinki declaration
Prospect There is a pressing need to develop a preventive strategy to depressive episodes during pregnancy and childbirth that is targeted cheap short-term and easy to implement Such work holds promise to positively affect womens mental health their families and importantly if successful may also improve long-term outcomes of the infants physical and mental health
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