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

This study has been completed.
Sponsor:
Collaborator:
Yale University
Information provided by (Responsible Party):
Kimberly Yonkers, Yale University
ClinicalTrials.gov Identifier:
NCT00965562
First received: August 24, 2009
Last updated: March 3, 2015
Last verified: February 2015
  Purpose

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.


Condition Intervention
Premenstrual Syndrome
Drug: Fluoxetine
Drug: Calcium
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-blind, Parallel Comparison of Fluoxetine, Calcium and Placebo for the Treatment of Moderate to Severe Premenstrual Syndrome (PMS)

Resource links provided by NLM:


Further study details as provided by Donaghue Medical Research Foundation:

Primary Outcome Measures:
  • Comparison of the Change in IDS Symptom Scores Among Groups [ Time Frame: over duration of treatment, 4 menstrual cycles averaging 4 months after baseline visit ] [ Designated as safety issue: No ]
    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.

  • Comparison of the Change in PMTS Symptom Scores Among Groups [ Time Frame: over duration of treatment, 4 menstrual cycles averaging 4 months after baseline visit ] [ Designated as safety issue: No ]
    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.

  • Comparison of the Change in CGI-S Symptom Scores Among Groups [ Time Frame: over duration of treatment, 4 menstrual cycles averaging 4 months after baseline visit ] [ Designated as safety issue: No ]
    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.

  • Comparison of the Change in DRSP Symptom Scores Among Groups [ Time Frame: over duration of treatment, 4 menstrual cycles averaging 4 months after baseline visit ] [ Designated as safety issue: No ]
    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.

  • Comparison of the Change in CGI Improvement Scores Among Groups [ Time Frame: over duration of treatment, 4 menstrual cycles averaging 4 months after baseline visit ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Proportion of Participants With DRSP LOCF Response to Treatment (50% Improvement) [ Time Frame: over duration of treatment, 4 menstrual cycles averaging 4 months after baseline visit ] [ Designated as safety issue: No ]
    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.

  • Proportion of Participants With IDS LOCF Response to Treatment (50% Improvement) [ Time Frame: over duration of treatment, 4 menstrual cycles averaging 4 months after baseline visit ] [ Designated as safety issue: No ]
    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.

  • Proportion of Participants With PMTS LOCF Response to Treatment (50% Improvement) [ Time Frame: over duration of treatment, 4 menstrual cycles averaging 4 months after baseline visit ] [ Designated as safety issue: No ]
    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.

  • Proportion of Participants With DRSP Visit-wise Response to Treatment (50% Improvement) [ Time Frame: over duration of treatment from baseline to visit 5, including 4 menstrual cycles averaging 4 months after baseline visit ] [ Designated as safety issue: No ]
    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.

  • Proportion of Patients With IDS Visit-wise Response to Treatment (50% Improvement) [ Time Frame: over duration of treatment from baseline to visit 5, including 4 menstrual cycles averaging 4 months after baseline visit ] [ Designated as safety issue: No ]

    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).


  • Proportion of Patients With PMTS Visit-wise Response to Treatment (50% Improvement) [ Time Frame: over duration of treatment from baseline to visit 5, including 4 menstrual cycles averaging 4 months after baseline visit ] [ Designated as safety issue: No ]
    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).


Enrollment: 49
Study Start Date: September 2000
Study Completion Date: October 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Prozac
Active Comparator: II
Calcium
Drug: Calcium
1200 mg of calcium to be taken for 5 menstrual cycles.
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.

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.

.

  Eligibility

Ages Eligible for Study:   18 Years to 48 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00965562

Locations
United States, Connecticut
Yale School of Medicine
New Haven, Connecticut, United States, 06510
Sponsors and Collaborators
Donaghue Medical Research Foundation
Yale University
Investigators
Principal Investigator: Kimberly A Yonkers, MD Yale School of Medicine
  More Information

No publications provided

Responsible Party: Kimberly Yonkers, Professor, Yale University
ClinicalTrials.gov Identifier: NCT00965562     History of Changes
Obsolete Identifiers: NCT00683605
Other Study ID Numbers: 0001011511
Study First Received: August 24, 2009
Results First Received: July 2, 2013
Last Updated: March 3, 2015
Health Authority: United States: Federal Government

Keywords provided by Donaghue Medical Research Foundation:
Premenstrual syndrome
PMS
calcium

Additional relevant MeSH terms:
Premenstrual Syndrome
Syndrome
Disease
Menstruation Disturbances
Pathologic Processes
Calcium, Dietary
Fluoxetine
Antidepressive Agents
Antidepressive Agents, Second-Generation
Bone Density Conservation Agents
Central Nervous System Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Serotonin Uptake Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on June 30, 2015