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

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

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.

Study Overview

• Status: Completed
• Conditions: Premenstrual Syndrome
• Intervention / Treatment: Drug: Fluoxetine; Drug: Calcium; Drug: Placebo

Detailed Description

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.

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• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 46 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: III	Drug: Placebo; 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.
Active Comparator: I; Fluoxetine	Drug: Fluoxetine; 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.; Other Names: Prozac
Active Comparator: II; Calcium	Drug: Calcium; 1200 mg of calcium to be taken for 5 menstrual cycles.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Donaghue Medical Research Foundation
• Collaborators: Yale University
• Investigators: Principal Investigator: Kimberly A Yonkers, MD, Yale School of Medicine

Study record dates

Study Major Dates

• Study Start: September 1, 2000
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): October 1, 2010

Study Registration Dates

• First Submitted: August 24, 2009
• First Submitted That Met QC Criteria: August 24, 2009
• First Posted (Estimate): August 25, 2009

Study Record Updates

• Last Update Posted (Estimate): March 23, 2015
• Last Update Submitted That Met QC Criteria: March 3, 2015
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Keywords: PMS; calcium; Premenstrual syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Menstruation Disturbances; Syndrome; Premenstrual Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Calcium-Regulating Hormones and Agents; Calcium; Fluoxetine
• Other Study ID Numbers: 0001011511