View Clinical Trial (Medical Research Study)
The Treatment of Menstrually-Related Mood Disorders With the Gonadotropin Releasing Hormone (GnRH) Agonist, Depot Leuprolide Acetate (Lupron)
| City: |
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Bethesda |
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Maryland |
| Zip Code: |
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20892 |
| Conditions: |
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PMDD - PMS - Depression |
| Purpose: |
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This study examines the effects of estrogen and progesterone on mood, the stress response,
and brain function and behavior in women with premenstrual syndrome.
Previously this study has demonstrated leuprolide acetate (Lupron(Registered Trademark)
(Registered Trademark)) to be an effective treatment for PMS. The current purpose of this
study is to evaluate how low levels of estrogen and progesterone (that occur during
treatment with leuprolide acetate) compare to menstrual cycle levels of estrogen and
progesterone (given during individual months of hormone add-back) on a variety of
physiologic measures (brain imaging, stress testing, etc.) in women with PMS.
PMS is a condition characterized by changes in mood and behavior that occur during the
second phase of the normal menstrual cycle (luteal phase). This study will investigate
possible hormonal causes of PMS by temporarily stopping the menstrual cycle with leuprolide
acetate and then giving, in sequence, the menstrual cycle hormones progesterone and
estrogen. The results of these hormonal studies will be compared between women with PMS and
healthy volunteers without PMS (see also protocol 92-M-0174).
At study entry, participants will undergo a physical examination. Blood, urine, and
pregnancy tests will be performed. Cognitive functioning and stress response will be
evaluated during the study along with brain imaging and genetic studies.
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| Study Summary: |
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This protocol is designed to accompany Clinical Protocol # 81-M-0126, The Phenomenology and
Biophysiology of Menstrually-Related Mood and Behavioral Disorders. Its original purposes
were as follows: 1) to evaluate the efficacy of the gonadotropin releasing hormone (GnRH)
agonist depot leuprolide acetate (Lupron) in the treatment of menstrually-related mood
disorders (MRMD) by determining whether mood and behavioral symptoms are eliminated when the
cyclic secretion of both gonadotropic hormones and gonadal steroids is suppressed, and 2) to
determine the possible relevance of gonadal steroids to affective state by sequentially
replacing estradiol and progesterone during continued GnRH suppression in those patients
whose premenstrual symptoms remit following administration of the GnRH agonist. We observed
that GnRH agonist induced ovarian suppression was an effective treatment compared to placebo
in women with MRMD. Additionally, women with MRMD but not asymptomatic controls
(participating in companion protocol 92-M-0174) experienced a recurrence of mood and
behavioral symptoms when either estradiol or progesterone (but not placebo) was added back.
These data suggest that women with MRMD have a differential sensitivity to the mood
destabilizing effects of gonadal steroids.
Having established that women with MRMD show a differential behavioral response to estrogen
and progesterone, we now hope to identify the underlying mechanisms and physiologic
concomitants of the differential behavioral sensitivity by performing studies (described in
companion protocols) under the three hormonal conditions created by this protocol, and
comparing results obtained with those seen in normal controls (Protocol #92-M-0174).
Planned studies include the following: cognitive testing, brain imaging (3D PET, FMRI, MRS)
and genetic studies including induced pluripotent cells.
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| Criteria: |
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- INCLUSION CRITERIA:
The subjects of this study will be women who meet the criteria for MRMD as described in
Protocol No. 81-M-0126, 'The Phenomenology and Biophysiology of Menstrually-related Mood
and Behavioral Disorders.' In brief, these criteria include:
1. history within the last two years of at least six months with menstrually-related
mood or behavioral disturbances of at least moderate severity--i.e., disturbances
that are distinct in appearance and associated with a notable degree of subjective
distress;
2. symptoms should have a sudden onset and offset;
3. age 18-50;
4. not pregnant and in good medical health;
5. medication free.
All patients participating in this protocol will have already participated in
Protocol No. 81-M-0126 and will have a prospectively confirmed and predictable
relationship between their mood disorder and the premenstrual phase of the menstrual
cycle, i.e., a 30% change in severity of symptom self rating scales, relative to the
range of the scale employed, during the seven days premenstrually compared with the
seven days post-menstrually in two out of three months of study.
The Schedule for Affective Disorders and Schizophrenia will be administered to all
patients prior to study entry. Any patient with a current axis I psychiatric
diagnosis will be excluded from participating in this protocol.
Prior to treatment, a complete physical and neurological examination will have been
performed and the following routine laboratory data obtained:
A. Blood
Complete blood count; thyroid function tests; cortisol; renal function tests, such as
BUN and creatinine; electrolytes; glucose; liver function tests.
B. Urine
Routine urinalysis; urine pregnancy test.
GnRH agonist will not be administered to any subject with significant clinical or
laboratory abnormalities. The blood tests and urinalysis will be repeated 2 weeks
after GnRH agonist administration to rule out any evidence of acute renal, hepatic or
hematologic toxicity.
Results of Pap smear performed within one year of the onset of treatment will be
obtained.
EXCLUSION CRITERIA:
The following conditions will constitute contraindications to treatment with hormonal
therapy and will preclude a subject's participation in this protocol:
- current Axis I psychiatric diagnosis
- history consistent with endometriosis,
- diagnosis of ill-defined, obscure pelvic lesions, particularly, undiagnosed
ovarian enlargement,
- hepatic disease as manifested by abnormal liver function tests,
- history of mammary carcinoma,
- history of pulmonary embolism or phlebothrombosis
- undiagnosed vaginal bleeding
- porphyria
- diabetes mellitus
- history of malignant melanoma
- cholecystitis or pancreatitis,
- cardiovascular or renal disease
- pregnancy
- Any woman meeting the Stages of Reproductive Aging Workshop Criteria (STRAW) for
the perimenopause. Specifically, we will exclude any woman with an elevated
plasma FSH level (> 14 IU/L) and with menstrual cycle variability of > 7 days
different from their normal cycle length.
- Subjects taking birth control pills will be excluded from the study.
- Subjects taking diuretics, prostaglandin inhibitors, or pyridoxine (putative
treatments for MRMD) will similarly be excluded from the study
- Patients taking psychotropic agents (e.g., lithium carbonate, tricyclic
antidepressants).
- All subjects will be required to use non-hormonal forms of birth control (e.g.,
barrier methods) to avoid pregnancy during this study.
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| NCT ID: |
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NCT00001259 |
| Primary Contact: |
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Principal Investigator
Peter J Schmidt, M.D.
National Institute of Mental Health (NIMH)
Peter J Schmidt, M.D.
Phone: (301) 496-6120
Email: PeterSchmidt@mail.nih.gov
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| Backup Contact: |
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N/A |
| Location Contact: |
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Bethesda, Maryland 20892
United States
Peter Schmidt, M.D.
Phone: 301-496-6120
Email: PeterSchmidt@mail.nih.gov
Site Status: Recruiting |
| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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May 17, 2013 |
| Modifications to this listing: |
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