Comparison of Fluoxetine, Calcium and Placebo for the Treatment of Moderate to Severe Premenstrual Syndrome (PMS)

Study Overview
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Brief Summary
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The purpose of this study is to compare the efficacy of calcium carbonate to fluoxetine in the treatment of moderate to severe PMS. Second, to compare each active agent to a placebo control. Third, to evaluate the efficacy of each treatment for specific symptom clusters (i.e. affective and somatic). Fourth, to determine whether the addition of calcium to on going fluoxetine treatment leads to additional therapeutic benefit.

Detailed Description
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This is a double blind, randomized, placebo controlled, parallel study that will randomize 60 women at the Yale site into treatment. Participants will be screened at various collaborating ob-gyn centers for possible PMS symptoms, and direct referrals from the community will also be accepted. Subject participation length is about 7 months with 6 scheduled study visits. Methodology: After successfully completing the screening and qualification phase, participants will be randomized to treatment at Visit 1 for 5 cycles of double-blind treatment. Participants will be evaluated monthly during the randomization phase for adverse events, concurrent medication, and primary and secondary efficacy variables. .

Official Title
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A Double-blind, Parallel Comparison of Fluoxetine, Calcium and Placebo for the Treatment of Moderate to Severe Premenstrual Syndrome (PMS)

Conditions
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Premenstrual Syndrome

Intervention / Treatment
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* Drug: Fluoxetine
* Drug: Calcium
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female outpatients between the ages of 18 and 48 who are: Menstruating Meet criteria for moderate to severe PMS Report PMS symptoms for at least 9 our of the 12 months prior to screening; 4) *Are using an adequate method of birth control. Exclusion Criteria: Any candidate who: Fulfills MINI (DSM-IV) criteria for a serious AXIS 1 disorder Fulfills DSM-IV criteria during the charting phase consistent with a diagnosis of psychotic disorder, bipolar disorder or major depressive disorder Has a severe, co-existing condition that, in the investigator's opinion, renders the patient unsuitable for the study Poses a significant risk of suicide Takes ongoing medication that could treat PMS symptoms Has a history of hypersensitivity or adverse reaction to fluoxetine or calcium Is lactating, pregnant or is planning to become pregnant during the course of the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 48 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: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: I<br>Fluoxetine | Drug: Fluoxetine<br>* Fluoxetine 20 mg per day for 4 menstrual cycles. For the fifth menstrual cycle, all women will receive calcium. Women on Fluoxetine will continue taking it in addition to 1200mg of calcium.<br>* Other names: Prozac;|
| Active Comparator: II<br>Calcium | Drug: Calcium<br>* 1200 mg of calcium to be taken for 5 menstrual cycles.<br>|
| Placebo Comparator: III<br> | Drug: Placebo<br>* For 5 cycles, women will receive placebo. At the end of the fourth cycle, all women will receive 1200 mg of calcium in addition to the placebo medication.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of the Change in IDS Symptom Scores Among Groups | IDS = Inventory of Depressive Symptomatology: measures depressive symptoms during the previous premenstrual phase with high internal consistency: sum of responses to 28 of 30 possible items each scored 0 to 3 points with total scoring (0=no symptoms, 84=most severe). This outcome is a measure of effect size between the two trial groups and the placebo group, with the placebo effect size value used as a reference. | over duration of treatment, 4 menstrual cycles averaging 4 months after baseline visit | 
| Comparison of the Change in PMTS Symptom Scores Among Groups | PMTS = Premenstrual Tension Syndrome (Observer Rating) Scale: a clinician-administered retrospective scale developed for the study of PMS, a sum of responses to 10 items each with 4 points (0=no symptoms, 40=most severe). This outcome is a measure of effect size between the two trial groups and the placebo group, with the placebo effect size value used as a reference. | over duration of treatment, 4 menstrual cycles averaging 4 months after baseline visit | 
| Comparison of the Change in CGI-S Symptom Scores Among Groups | CGI-S = Clinical Global Impression-Severity: a severity scale widely used in psychopharmacology research (1=normal not at all ill, 7=among most extremely ill). This outcome is a measure of effect size between the two trial groups and the placebo group, with the placebo effect size value used as a reference. | over duration of treatment, 4 menstrual cycles averaging 4 months after baseline visit | 
| Comparison of the Change in DRSP Symptom Scores Among Groups | DRSP = Daily Record of Severity of Problems, which combines responses to 21 items each with scale: 1=no symptoms, 6=extreme. This outcome is a measure of effect size between the two trial groups and the placebo group, with the placebo effect size value used as a reference. | over duration of treatment, 4 menstrual cycles averaging 4 months after baseline visit | 
| Comparison of the Change in CGI Improvement Scores Among Groups | CGI-I = Clinical Global Impression Improvement: the improvement subscale of CGI measuring change at each visit as compared to visit 1 (1=very much improved, 7=very much worse). This outcome is a measure of effect size between the two trial groups and the placebo group, with the placebo effect size value used as a reference. | over duration of treatment, 4 menstrual cycles averaging 4 months after baseline visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants With DRSP LOCF Response to Treatment (50% Improvement) | DRSP: Daily Record of Severity of Problems, which combines responses to 21 items each with scale: 1=no symptoms, 6=extreme. LOCF: the last observation carried forward. | over duration of treatment, 4 menstrual cycles averaging 4 months after baseline visit | 
| Proportion of Participants With IDS LOCF Response to Treatment (50% Improvement) | IDS: Inventory of Depressive Symptomatology: measures depressive symptoms during the previous premenstrual phase with high internal consistency: sum of responses to 28 of 30 possible items each scored 0 to 3 points with total scoring (0=least severe, 84=most severe). LOCF: last observation carried forward. | over duration of treatment, 4 menstrual cycles averaging 4 months after baseline visit | 
| Proportion of Participants With PMTS LOCF Response to Treatment (50% Improvement) | PMTS: Premenstrual Tension Syndrome (Observer Rating) Scale: a clinician-administered retrospective scale developed for the study of PMS, a sum of responses to 10 items each with 4 points (0=no symptoms, 40=most severe). LOCF: last observation carried forward. | over duration of treatment, 4 menstrual cycles averaging 4 months after baseline visit | 
| Proportion of Participants With DRSP Visit-wise Response to Treatment (50% Improvement) | Visit-wise response considers participants who remained in the study until Visit 5 and provided data for the visit. DRSP = Daily Record of Severity of Problems, which combines responses to 21 items each with scale: 1=no symptoms, 6=extreme. | over duration of treatment from baseline to visit 5, including 4 menstrual cycles averaging 4 months after baseline visit | 
| Proportion of Patients With IDS Visit-wise Response to Treatment (50% Improvement) | Visit-wise response considers participants who remained in the study until Visit 5 and provided data for the visit. IDS = Inventory of Depressive Symptomatology: measures depressive symptoms during the previous premenstrual phase with high internal consistency, sum of responses to 28 of 30 possible items each scored 0 to 3 points with total scoring (0=no symptoms, 84=most severe). | over duration of treatment from baseline to visit 5, including 4 menstrual cycles averaging 4 months after baseline visit | 
| Proportion of Patients With PMTS Visit-wise Response to Treatment (50% Improvement) | Visit-wise response considers participants who remained in the study until Visit 5 and provided data for the visit. PMTS = Premenstrual Tension Syndrome (Observer Rating) Scale: a clinician-administered retrospective scale developed for the study of PMS, a sum of responses to 10 items each with 4 points (0=no symptoms, 40=most severe). | over duration of treatment from baseline to visit 5, including 4 menstrual cycles averaging 4 months after baseline visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PMS, Premenstrual syndrome, calcium