Citalopram in Treating Postmenopausal Women With Hot Flashes

Study Overview
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Brief Summary
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RATIONALE: Citalopram may help relieve hot flashes in women who had or have not had breast cancer. It is not yet known which dose of citalopram is more effective in treating hot flashes in postmenopausal women. PURPOSE: This randomized phase III trial is studying three different doses of citalopram to compare how well they work in treating postmenopausal women with hot flashes.

Detailed Description
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OBJECTIVES: Primary Evaluate the efficacy of three different doses of citalopram hydrobromide on hot flash scores in postmenopausal women with a history of breast cancer or in postmenopausal women who do not wish to take estrogen replacement therapy for fear of increased risk of breast cancer. Secondary Compare the side effect profile of these regimens in these patients. Compare the effects of these regimens on the secondary outcome of mood and interference with activities from hot flashes. Determine if CYP2C19 and CYP2D6 polymorphisms predict efficacy of various doses of citalopram hydrobromide. OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to age (18-49 years vs ≥ 50 years), tamoxifen (yes vs no), selective estrogen-receptor modulators (SERMs) (yes vs no), aromatase inhibitors (yes vs no), duration of hot flashes (< 9 months vs ≥ 9 months), and frequency of hot flashes per day (< 4 vs 4-9 vs ≥ 10). Patients are randomized to 1 of 4 treatment arms. Arm I (low-dose citalopram hydrobromide): Patients receive 1 tablet of oral citalopram once daily in weeks 2-7. Arm II (medium-dose citalopram hydrobromide): Patients receive 1 tablet of oral citalopram once daily in week 2 and 2 tablets once daily in weeks 3-7. Arm III (high-dose citalopram hydrobromide): Patients receive 1 tablet of oral citalopram once daily in week 2, 2 tablets once daily in week 3, and 3 tablets once daily in weeks 4-7. Arm IV (placebo): Patients receive 1-3 placebo tablets once daily in weeks 2-7. All patients complete a diary of hot flash incidence in weeks 1-7 and undergo blood collection periodically during study treatment for translational research studies. A Symptom Experience diary is completed weekly and Profile of Mood States and Hot Flash-Related Interference Scale questionnaires are completed at baseline and in week 7.

Official Title
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Phase III Randomized, Double-Blind, Placebo-Controlled Evaluation of Citalopram for the Treatment of Hot Flashes

Conditions
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Breast Cancer, Hot Flashes, Psychosocial Effects of Cancer and Its Treatment

Intervention / Treatment
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* Drug: citalopram hydrobromide
* Other: placebo


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Must meet 1 of the following criteria: History of breast cancer No current malignant disease No history of breast cancer and refused estrogen replacement therapy due to perceived increased risk of breast cancer Bothersome hot flashes, defined as hot flashes ≥ 14 times/week and of sufficient severity to make the patient desire therapeutic intervention Presence of hot flashes ≥ 1 month prior to study entry Hormone receptor status not specified PATIENT CHARACTERISTICS: Female Postmenopausal, as defined by 1 of the following criteria: Absence of a menstrual period in the past 12 months Bilateral oophorectomy Absence of a menstrual period in the past 6 months with follicle-stimulating hormone (FSH) level > 40 mIU/mL ECOG performance status 0-1 Life expectancy ≥ 6 months Willing to provide blood samples during study participation No history of allergic or other adverse reactions to citalopram hydrobromide or other selective serotonin reuptake inhibitors (SSRIs) No documented mania or hypomania PRIOR CONCURRENT THERAPY: At least 4 weeks since prior and no concurrent antineoplastic chemotherapy At least 4 weeks since prior and no concurrent androgens, estrogens, or progestational agents At least 3 months since prior antidepressant use, including Hypericum perforatum (St. John's wort) Concurrent tamoxifen, raloxifene, or aromatase inhibitors allowed if on a constant dose for ≥ 4 weeks and continuing medication during study period No other concurrent or planned agents for treating hot flashes (e.g., phenobarbital, megestrol, or clonidine) Stable dose of vitamin E allowed as long as it was started > 30 days prior to study entry Concurrent soy allowed Concurrent gabapentin allowed for reasons other than hot flashes if on a constant dose for ≥ 1 month and continuing during study period

Ages Eligible for Study
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Minimum Age: 18 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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: low-dose citalopram hydrobromide<br>Patients receive 1 tablet of oral citalopram once daily in weeks 2-7. All patients complete a diary of hot flash incidence in weeks 1-7 and undergo blood collection periodically during study treatment for translational research studies. | Drug: citalopram hydrobromide<br> <br> |
| Experimental: medium-dose citalopram hydrobromide<br>Patients receive 1 tablet of oral citalopram once daily in week 2 and 2 tablets once daily in weeks 3-7. All patients complete a diary of hot flash incidence in weeks 1-7 and undergo blood collection periodically during study treatment for translational research studies. | Drug: citalopram hydrobromide<br> <br> |
| Experimental: high-dose citalopram hydrobromide<br>Patients receive 1 tablet of oral citalopram once daily in week 2, 2 tablets once daily in week 3, and 3 tablets once daily in weeks 4-7. All patients complete a diary of hot flash incidence in weeks 1-7 and undergo blood collection periodically during study treatment for translational research studies. | Drug: citalopram hydrobromide<br> <br> |
| Placebo Comparator: placebo<br>Patients receive 1-3 placebo tablets once daily in weeks 2-7. All patients complete a diary of hot flash incidence in weeks 1-7 and undergo blood collection periodically during study treatment for translational research studies. | Other: placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in average hot flash score from baseline until week 7 of treatment |  | Up to 7 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity |  | Up to 7 weeks | 
| Mood- and hot flash-related daily interference with activities |  | Up to 7 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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psychosocial effects of cancer and its treatment, hot flashes, breast cancer