Ignite Creation Date:
2024-05-05 @ 11:41 AM
Last Modification Date:
2024-10-26 @ 9:11 AM
Study NCT ID:
NCT00100360
Status:
COMPLETED
Last Update Posted:
2018-07-05
First Post:
2004-12-29
Brief Title:
Hormonal Causes of Menstrual-Related Mood Disorders
Sponsor:
National Institute of Mental Health NIMH
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
5HT1A and SERT Imaging During Pharmacologically Induced Hypogonadotropic Hypogonadism With and Without Estrogen and Progesterone Replacement
Status:
COMPLETED
Status Verified Date:
2016-12-15
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:
None
Brief Summary:
This study will explore possible hormonal causes of menstrual-related mood disorders MRMD by stopping the menstrual cycle with a drug called Lupron and then giving in sequence two menstrual cycle hormones progesterone and estrogen The study will first evaluate Luprons effectiveness in treating MRMD and will then examine the effects of giving estrogen and progesterone on mood and behavior In addition positron emission tomography PET and magnetic resonance imaging MRI will be used to study serotonin receptors and transporters - molecules in the brain that are thought to play a major role in mood changes related to the menstrual cycle
Menstruating women between 18 and 50 years of age who are in good health not pregnant and not taking medications may be eligible for this study Women with MRMD must have had at least moderately severe MRMD or behavioral disturbances for at least 6 months within 2 years of entering the study Healthy controls must have no history of MRMD or behavioral disturbances Candidates undergo physical and neurological examinations chest x-ray electrocardiogram and blood and urine tests Results of a recent Pap smear no longer than 12 months before beginning the study must be available
Participants undergo the following tests and procedures
Drug treatment Lupron is injected into a muscle once a month for 5 months After the second month participants receive estrogen or progesterone or both daily Estrogen is delivered through a skin patch 20 micrograms per day and the progesterone is taken as a rectal or vaginal suppository twice a day for the remaining 12 weeks of the study Every day all participants wear a skin patch and insert two suppositories but at some point during the 12 weeks active medication is replaced with placebo to allow the drugs to wash out of the body
Physical examination and blood draw A physical examination and blood tests are done at the start of the study and several times during the study to assess general health evaluate liver and kidney function and measure blood cell counts
Response to treatment drugs Responses to Lupron estrogen and progesterone are evaluated periodically with interviews and symptoms self-rating scales Control subjects also take paper and pencil psychological tests
PET imaging A total of six PET scans are done at three time points during hormone treatment PET uses small amounts of a radioactive chemical called a tracer that labels active areas of the brain For the procedure the subject lies on the scanner bed A special mask is fitted to the head and attached to the bed to help keep the subjects head still during the scan so the images will be clear A brief scan is done just before the radioactive tracer is injected to help in analyzing the PET data After the tracer is injected through a catheter plastic tube placed in the arm pictures are taken for about 2 hours during which the subject lies still on the scanner bed
MRI scan MRI uses a magnetic field and radio waves to produce images of body tissues and organs For this procedure the patient lies on a table that is moved into the scanner a narrow cylinder and wears earplugs to muffle loud knocking and thumping sounds that occur during the scanning process The procedure lasts about 1 hour
Menstruating women between 18 and 50 years of age who are in good health not pregnant and not taking medications may be eligible for this study Women with MRMD must have had at least moderately severe MRMD or behavioral disturbances for at least 6 months within 2 years of entering the study Healthy controls must have no history of MRMD or behavioral disturbances Candidates undergo physical and neurological examinations chest x-ray electrocardiogram and blood and urine tests Results of a recent Pap smear no longer than 12 months before beginning the study must be available
Participants undergo the following tests and procedures
Drug treatment Lupron is injected into a muscle once a month for 5 months After the second month participants receive estrogen or progesterone or both daily Estrogen is delivered through a skin patch 20 micrograms per day and the progesterone is taken as a rectal or vaginal suppository twice a day for the remaining 12 weeks of the study Every day all participants wear a skin patch and insert two suppositories but at some point during the 12 weeks active medication is replaced with placebo to allow the drugs to wash out of the body
Physical examination and blood draw A physical examination and blood tests are done at the start of the study and several times during the study to assess general health evaluate liver and kidney function and measure blood cell counts
Response to treatment drugs Responses to Lupron estrogen and progesterone are evaluated periodically with interviews and symptoms self-rating scales Control subjects also take paper and pencil psychological tests
PET imaging A total of six PET scans are done at three time points during hormone treatment PET uses small amounts of a radioactive chemical called a tracer that labels active areas of the brain For the procedure the subject lies on the scanner bed A special mask is fitted to the head and attached to the bed to help keep the subjects head still during the scan so the images will be clear A brief scan is done just before the radioactive tracer is injected to help in analyzing the PET data After the tracer is injected through a catheter plastic tube placed in the arm pictures are taken for about 2 hours during which the subject lies still on the scanner bed
MRI scan MRI uses a magnetic field and radio waves to produce images of body tissues and organs For this procedure the patient lies on a table that is moved into the scanner a narrow cylinder and wears earplugs to muffle loud knocking and thumping sounds that occur during the scanning process The procedure lasts about 1 hour
Detailed Description:
The central serotonergic 5HT system is one of the candidate systems that may mediate the abnormal mood and behavioral response to ovarian steroids observed in women with menstrual-related mood disorders MRMD Numerous studies have attempted to measure 5HT system function in women with MRMD and controls however previous studies were restricted to the evaluation of indirect measures of 5HT function eg platelet 5HT uptake or responses to serotonergic pharmacologic challenges Radioligand imaging of specific components of the 5HT system currently represents the most direct measure of central serotonergic function available In this study we will image serotonergic measures during pharmacological conditions previously demonstrated to induce a remission and a subsequent provocation of mood symptoms in women with MRMD but not controls
This protocol has two outcome measures 5HT1A binding and SERT binding two groups of subjects women with MRMD and controls and three distinct hormonal conditions hypogonadism estrogen replacement and progesterone replacement Our principal aim in this study is to investigate differences in the outcome measures in women with MRMD compared to controls Our primary hypothesis is that 5HT1A binding will be decreased and SERT binding will be increased in women with MRMD A secondary hypothesis is that women with MRMD but not controls will display reproductive steroid modulation of 5HT1A and SERT binding This study will help test existing hypotheses about the pathophysiologic relevance of serotonin function in MRMD and the role of reproductive steroids in serotonergic regulation First we selected 5HT1A receptor binding as an outcome measure for the following reasons 5HT1A function is modulated by both estradiol and progesterone abnormalities of 5HT1A binding have been reported in both depressive and anxiety disorders as well as possibly MRMD 5HT1A receptors have been identified as potential mediators of estradiols antidepressant-like effects in the forced swim test and the 5HT1A system is involved in the regulation of GABA activity abnormalities of which have been implicated in MRMD Second we selected SERT binding as an outcome measure for the following reasons selective serotonin reuptake inhibitors but not traditional antidepressants are effective treatments for MRMD abnormalities of SERT binding have been reported in depressive disorders in women preliminary data suggest that women with MRMD are characterized by an elevated frequency of the long more transcriptionally active polymorphism of the serotonin transporter 5HTTLPR Roca et al women with MRMD have altered imipramine binding and platelet 5HT uptake compared to controls as well as altered platelet paroxetine binding which normalize with successful treatment with GnRH agonist and finally SERT message binding and protein have been reported to be changed by ovarian steroids in preclinical studies
We hypothesize that the effects of hormonal condition on 5HT1A receptor binding will differ in patients and controls Specifically we anticipate that 5HT1A binding will be decreased in hippocampus and prefrontal cortex in patients with MRMD but not controls Such a decrease if a trait characteristic will be demonstrable irrespective of hormonal state However as symptoms of MRMD are directly precipitated by estradiol or progesterone see below it is possible that symptoms are accompanied by state and steroid-dependent changes in 5HT1A binding and function Consequently our secondary hypothesis is that estradiol or progesterone induces changes in 5HT1A receptor binding in women with MRMD but not in control women
Similarly we hypothesize that women with MRMD will have increased SERT binding activity compared to controls consistent with the therapeutic efficacy of selective serotonin reuptake inhibitors in this condition However a secondary hypothesis is that estradiol or progesterone-induced changes in SERT binding will occur in a hormone-dependent and mood state-dependent manner Specifically consistent with the literature in rodents acute changes in ovarian steroids will increase SERT binding in association with the induction of symptoms in women with MRMD but not controls
This protocol has two outcome measures 5HT1A binding and SERT binding two groups of subjects women with MRMD and controls and three distinct hormonal conditions hypogonadism estrogen replacement and progesterone replacement Our principal aim in this study is to investigate differences in the outcome measures in women with MRMD compared to controls Our primary hypothesis is that 5HT1A binding will be decreased and SERT binding will be increased in women with MRMD A secondary hypothesis is that women with MRMD but not controls will display reproductive steroid modulation of 5HT1A and SERT binding This study will help test existing hypotheses about the pathophysiologic relevance of serotonin function in MRMD and the role of reproductive steroids in serotonergic regulation First we selected 5HT1A receptor binding as an outcome measure for the following reasons 5HT1A function is modulated by both estradiol and progesterone abnormalities of 5HT1A binding have been reported in both depressive and anxiety disorders as well as possibly MRMD 5HT1A receptors have been identified as potential mediators of estradiols antidepressant-like effects in the forced swim test and the 5HT1A system is involved in the regulation of GABA activity abnormalities of which have been implicated in MRMD Second we selected SERT binding as an outcome measure for the following reasons selective serotonin reuptake inhibitors but not traditional antidepressants are effective treatments for MRMD abnormalities of SERT binding have been reported in depressive disorders in women preliminary data suggest that women with MRMD are characterized by an elevated frequency of the long more transcriptionally active polymorphism of the serotonin transporter 5HTTLPR Roca et al women with MRMD have altered imipramine binding and platelet 5HT uptake compared to controls as well as altered platelet paroxetine binding which normalize with successful treatment with GnRH agonist and finally SERT message binding and protein have been reported to be changed by ovarian steroids in preclinical studies
We hypothesize that the effects of hormonal condition on 5HT1A receptor binding will differ in patients and controls Specifically we anticipate that 5HT1A binding will be decreased in hippocampus and prefrontal cortex in patients with MRMD but not controls Such a decrease if a trait characteristic will be demonstrable irrespective of hormonal state However as symptoms of MRMD are directly precipitated by estradiol or progesterone see below it is possible that symptoms are accompanied by state and steroid-dependent changes in 5HT1A binding and function Consequently our secondary hypothesis is that estradiol or progesterone induces changes in 5HT1A receptor binding in women with MRMD but not in control women
Similarly we hypothesize that women with MRMD will have increased SERT binding activity compared to controls consistent with the therapeutic efficacy of selective serotonin reuptake inhibitors in this condition However a secondary hypothesis is that estradiol or progesterone-induced changes in SERT binding will occur in a hormone-dependent and mood state-dependent manner Specifically consistent with the literature in rodents acute changes in ovarian steroids will increase SERT binding in association with the induction of symptoms in women with MRMD but not controls
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 05-M-0059 | None | None | None |