Evaluation of Safety/Efficacy of Diagnostic Skin Test Panel and Desensitization Hormone Kit for Treatment of Premenstrual Syndrome (PMS)

Study Overview
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Brief Summary
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The EVE-PMS technology is intended for determination of intolerance or sensitivity to sex hormones, among women suffering from severe PreMenstrual Syndrome (PMS) and desensitizes them with the relevant sex hormones in order to reduce PMS symptoms. The system includes skin testing panel for identification of hormones to which the patients might be sensitive. Tests are applied close to the ovulation period and the skin reaction is examined in 20 minutes, 48 hours and daily during the following month. Results of skin tests and patient's history will determine the eligibility of the patients to enter a desensitization protocol. During the desensitization period hormones to which the patient were found sensitive to, are injected intradermally three times (once a month) within the luteal phase in increasing doses. The end-point of the study is a statistically significant decrease, or elimination of PMS symptoms, compared to a solvent group.

Official Title
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A Phase II Randomized, Two-arms, Single-blind, Cross Controlled Study for Evaluation the Safety and Efficacy of Diagnosis and Treatment of Premenstrual Syndrome by Detecting Skin Reactions Followed by Desensitization to Sex Hormones

Conditions
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Premenstrual Syndrome

Intervention / Treatment
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* Drug: Skin test panel and desensitization kit
* Drug: Skin test panel and solvent


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Person is over the age of 20 but not older than age 45. Person is willing to participate as evidenced by signing the written informed consent form. Suffers from known dominant severe symptom of breast swelling and tenderness (level 7-10 according to standard scale of PMS symptoms severity) Other severe symptoms of Premenstrual syndrome (based on WHO and ACOG criteria). This may include one or more of PMS symptoms with level 7-10 according to standard scale of PMS symptoms severity. At work, school, home, or in daily routine, at least one of the PMS symptoms caused reduction of productivity or inefficiency At least one of the PMS symptoms caused avoidance of or less participation in hobbies or social activities At least one of the PMS symptoms interfere with relationships with others Timing of PMS symptom(s): during the 14 days prior to onset of menstrual flow (rather than spotting) and up to 5 days during the menstrual flow. Pattern and length of PMS symptomatic period: minimum of 2 days, up to 14 days. For PMS diagnosis two out of last three consecutive menstrual cycles were monitored by daily monitoring of symptoms. Timing and length of asymptomatic phase: day 6 to at least day 10 of the menstrual cycle. Cyclicity - presentation of the 'off-on' phenomenon: there should be a clear shift from no PMS symptoms to PMS symptoms. Reliable non hormonal contraception. Exclusion Criteria: Pregnant or lactating woman Oral contraceptives during last three months, including hormonal IUD (trade name mirena). Serious health problems. Unexplained menstrual disorders. Treated by hormones (estrogen and progesterone).

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Hormones<br> | Drug: Skin test panel and desensitization kit<br>* Skin testing 4 sex hormones will be performed during the luteal phase of the subject's menstrual cycle by study investigators. Hormones: Progesterone 1mmol/L; Estradiol 1mmol/L; Estrone 3mmol/L; Estriol 3mmol/L Controls: Saline (NaCl) 0.9%; Ethyl Oleate with 10% Benzyl Alcohol; Histamine phosphate 1mg/ml (epicutaneous- prick test) Patients with positive skin test to at least one sex hormone will be injected with an increasing volume of the appropriate hormone at the same concentration as it was used in the skin test as follows: Week 4th of the study (luteal phase of 2nd menstrual cycle) - 0.04 ml Week 8th of the study (luteal phase of 3rd menstrual cycle) - 0.08 ml Week 12th of the study (luteal phase of 4th menstrual cycle) - 0.16 ml<br>* Other names: Estriol;|
| Placebo Comparator: Solvent<br> | Drug: Skin test panel and solvent<br>* Skin testing 4 sex hormones will be performed during the luteal phase of the subject's menstrual cycle by study investigators. Hormones: Progesterone 1mmol/L; Estradiol 1mmol/L; Estrone 3mmol/L; Estriol 3mmol/L Controls: Saline (NaCl) 0.9%; Ethyl Oleate with 10% Benzyl Alcohol; Histamine phosphate 1mg/ml (epicutaneous- prick test) Patients with positive skin test to at least one sex hormone will be injected with an increasing volume of the solvent as follows: Week 4th of the study (luteal phase of 2nd menstrual cycle) - 0.04 ml Week 8th of the study (luteal phase of 3rd menstrual cycle) - 0.08 ml Week 12th of the study (luteal phase of 4th menstrual cycle) - 0.16 ml<br>* Other names: Estriol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the efficacy of hormonal desensitization compared to solvent treatment in reduction of the PMS symptoms severity and length of PMS by subjects with severe PMS symptoms (according to criteria of PMS). |  | 5-6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the efficacy of hormonal desensitization compared to solvent treatment in reduction of the breast swelling and tenderness in 4 weeks of treatment. |  | 2-3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PreMenstrual Syndrome, Hormones, Skin tests, Desensitization, Allergen Immunotherapy