EnBrace HR for PMS With Prominent Mood Symptoms or Menstrual Related Mood Disorders
EnBrace HR for PMS With Prominent Mood Symptoms or Menstrual Related Mood Disorders
The purpose of this study is to assess a novel nutritional supplement developed for prenatal
 health and mood benefits, and to determine whether there is preliminary evidence for efficacy
 in Menstrual Related Mood Disorders (MRMD), including PMS with Prominent Mood Symptoms and
 PMDD.
The luteal phase of the menstrual cycle, also referred to as the premenstrual phase, is a
 time of vulnerability for women, during which many suffer from a number of physical and
 psychiatric symptoms. Premenstrual mood symptoms affect a great proportion of women, and can
 affect general wellbeing, self-esteem, occupational and social functioning, and
 relationships. A spectrum of severity exists around the manifestation of these symptoms, and
 a range of terms can be used to refer to women with substantial psychiatric morbidity around
 the luteal phase of the menstrual cycle.

 Premenstrual Dysphoric Disorder (PMDD) has been formalized as a psychiatric diagnosis and
 added to the DSM-5. For a diagnosis of PMDD, the diagnostic criteria include the following
 and must be met for most menstrual cycles in the preceding year: A) In the majority of
 cycles, at least five symptoms must be present in the final week before the onset of menses
 and start to improve within a few days of its onset, B) One or more of the following must be
 present: 1) affective lability, 2) irritability/anger or increased interpersonal conflicts,
 3) depressed mood, hopelessness or self-deprecating thoughts, 4) anxiety or tension. Also,
 one or more of the following must be present: 1) decreased interest in usual activities, 2)
 difficulty concentrating, 3) low energy or fatigue, 4) change in appetite or cravings, 5)
 increased or decreased sleep, 6) feeling overwhelmed or out of control, 7) physical symptoms
 (i.e., breast tenderness, bloating, weight gain).

 Several overlapping definitions and terms capture psychiatric distress related to the luteal
 phase of the menstrual cycle. Many women suffer substantially during the premenstrual phase
 but do not have symptoms that fully meet criteria for PMDD. The term menstrual related mood
 disorder (MRMD) has been used to describe conditions that include Premenstrual Dysphoric
 Disorder (PMDD) and also mood dysregulation related to the menstrual cycle that is clinically
 substantial but where the threshold for a PMDD formal diagnosis is not met. Premenstrual
 Syndrome (PMS) refers to recurrent premenstrual symptoms that may include mood symptoms, but
 mood symptoms may not be present in all women with PMS.Therefore, a subset of women with PMS
 with prominent (or marked) mood symptoms would be included under the category of MRMD.
 Therefore, in addition to those who meet full criteria for PMDD, many women suffer from
 premenstrual syndrome (PMS) with prominent mood symptoms. The term menstrual related mood
 disorder (MRMD), applies to women who may or may not meet the threshold for the formal PMDD
 diagnoses and represents a great number of women of reproductive age who suffer on a regular
 basis from luteal phase mood symptoms that compromise quality of life.

 Previous pre-clinical or clinical studies leading up to and supporting the research The
 prevalence of PMDD is between 3-8% of menstruating women; in addition, another 10-11%
 experience PMS with Prominent Mood Symptoms.1 Based on these estimates, 13-19% of
 menstruating women experience MRMD, including those with both PMDD and PMS with prominent
 mood symptoms, on a consistent basis.

 Menstrual related mood disorders (MRMDs) are characterized by prominent symptoms during the
 luteal phase of the cycle, with relief starting with the onset of menses or soon after menses
 start. The follicular phase is generally asymptomatic, and the difference in symptom
 expression between worsening during the luteal phase and improvement during the follicular
 phase is its hallmark. While many women recognize these patterns of cyclic mood worsening and
 the impact upon quality of life, many women do not seek treatment. For women who do seek
 treatment from health care providers, the first line pharmacologic treatments are
 serotonergic antidepressants and oral contraceptive pills. For women who prefer other
 options, such as complementary and alternative medicine treatments or nutritional approaches,
 few treatments have received rigorous study. There is some promising but limited research
 with integrative treatments, such as light therapy, supplements, and herbal treatments.

 Objective: To evaluate the efficacy of EnBrace HR when used to treat premenstrual syndromes
 (PMS) with predominant mood symptoms, also referred to as MRMD.

 Specific Aim 1: To evaluate the effect of treatment with EnBrace HR in women with prominent
 mood symptoms in the premenstrual phase of the menstrual cycle. EnBrace will be administered
 in a continuous daily regimen, and the outcome will be the effect on the mean DRSP during the
 luteal phase from baseline to the treatment cycle 1 and 2 assessments.

 Exploratory Aims: To evaluate the effect of EnBrace HR with respect to:

 1. Mean change from baseline to endpoint in CGI-S scores

 2. Tolerability and safety

 3. To assess whether biomarkers can be identified that appear to be associated with
 treatment response to EnBrace HR

 The current study will provide evidence regarding the efficacy, tolerability, feasibility and
 acceptability of a selected non-psychotropic treatment alternative to serotonergic
 antidepressants and oral contraceptive pills. We hypothesize that the prevalence of PMDD,
 MRMD, and PMS in menstruating women may be attenuated if there are other effective treatments
 available to women.
Inclusion Criteria:

 1. Regular menstrual cycles, 23-35 days in length.

 2. MRMD diagnosis based on the DRSP items, with: at least 1 or more core symptoms
 occurring during the luteal phase of the menstrual cycle for at least the past three
 months by patient history, including: 1) low mood, 2) hopelessness, 3) feeling
 worthless or guilty, 4) feeling anxious or "keyed up" or "on edge," 5) mood swings, 6)
 more sensitive to rejection or to hurt feelings, 7) feeling angry/irritable, or 8)
 having interpersonal conflicts.

 3. Patients must also have at least 1 associated symptom on the DRSP that is not
 considered a core symptom that occurs during the luteal/premenstrual phase of the
 menstrual cycle.

 4. Currently experiencing clinically significant MRMD symptoms, defined as ≥ 30% increase
 in the total Daily Record of Severity of Problems Scale (DRSP) score from the
 mid-follicular phase (average of DRSP scores for days 6-10) to the late-luteal phase
 (average of DRSP scores for last 5 days prior to menstrual bleeding).

 5. Negative serum Human Chorionic Gonadotropin (HCG) at baseline, and negative urine HCG
 at visits 3 and 5.

 6. Willingness to use adequate contraceptive methods during the study, if sexually
 active. Hormonal contraceptives are allowed if the premenstrual symptoms still meet
 study criteria despite use and patient has been on a stable regimen for >3 months.

 7. Good general health.

 Exclusion Criteria:

 1. Amenorrhea or irregular menstrual periods (defined as unable to predict within 7 days)
 during past 2 months.

 2. Pregnant and lactating women.

 3. Women taking a prenatal vitamin, methotrexate, fluorouracil, colchicine,
 bromocriptine, Gonadotropin-Releasing Hormone (GnRH) agonists, vitamin B6 (>100 mg),
 calcium supplements (>1500 mg per day), or para-aminosalicylic acid.

 4. Significant risk for self-harm or harm to others.

 5. Meet criteria for a primary diagnosis of schizophrenia, bipolar disorder, an active
 eating disorder of anorexia or bulimia, dementia, delirium, or other cognitive
 disorder.

 6. Current major depressive episode or anxiety disorder that is a primary focus of
 current treatment. Patients may be on an antidepressant used for maintenance treatment
 if the dose is not changed intermittently to address premenstrual symptoms; dose must
 be stable for at least 8 weeks prior to study entry.

 7. Presence of an active substance and/or alcohol abuse disorder within six months prior
 to screening.

 8. Known low B12 levels, pPernicious anemia or history of gastric bypass surgery or
 bariatric surgery.

 9. Seizure disorder or current use of an anticonvulsant medication

 10. Allergy to beeswax, soy, fish, nuts, peanuts, egg, wheat, milk, and/or shellfish.

 11. Non-English speaking.