Evaluation of SAMe for Hot Flashes

Study Overview
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Brief Summary
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RATIONALE: S-adenosyl-L-methionine may help relieve hot flashes in women based upon its ability to potentially modulate serotonin. PURPOSE: This phase II trial is studying the side effects and how well s-adenosyl-L-methionine works in treating hot flashes in women with a history of breast cancer or those who do not wish to take estrogen due to a perceived increased risk of breast cancer.

Detailed Description
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OBJECTIVES: I. To evaluate the impact of SAMe on hot flash scores in women with a history of breast cancer or women who do not wish to take estrogen therapy for fear of increased risk of breast cancer. II. To evaluate the toxicity of SAMe in this study population. III. To evaluate the effect of SAMe using quality-of-life (QOL) measures. OUTLINE: During the first week, participants will complete a daily, prospective hot flash diary and complete baseline questionnaires and will not be taking any study medication. After this baseline week, participants will receive oral s-adenosyl-L-methionine, 400 mg, once daily on days 8-14 and twice daily on days 15-49 in the absence of unacceptable toxicity.

Official Title
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Phase II Evaluation of S-Adenosyl-L-Methionine (SAMe) for the Treatment of Hot Flashes

Conditions
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Healthy, no Evidence of Disease, Hot Flashes

Intervention / Treatment
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* Drug: S-adenosyl-L-methionine disulfate p-toluene-sulfonate
* Other: questionnaire administration
* Procedure: quality-of-life assessment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women with a history of breast cancer (currently without malignant disease) or women who have no history of breast cancer but who wish to avoid estrogen due to a perceived increased risk of breast cancer Bothersome hot flashes (defined by their occurrence >= 14 times per week and of sufficient severity to make the patient desire therapeutic intervention) Presence of hot flashes for >= 1 month prior to registration Life expectancy >= 6 months Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1 Ability to complete questionnaire(s) by themselves or with assistance Negative pregnancy test done =< 7 days prior to registration for women of childbearing potential only Exclusion Criteria: Any of the following current (=< last 4 weeks) or planned therapies (tamoxifen, raloxifene, or aromatase inhibitors are allowed, but the patient must have been on a constant dose for >= 4 weeks and must not be expected to stop the medication during the study period): antineoplastic chemotherapy, androgens, estrogens, progestational agents, other herbal supplements, including soy, vitamin E, flaxseed, and megadose vitamins (herbal teas, multivitamins, and vitamin D are allowed), warfarin (1 mg of daily warfarin is allowed for central line patency), medications interacting with SAMe (antidepressants, monoamine oxidase (MAO) inhibitors, meperidine, dextromethorphan, pentazocine, tramadol, gabapentin, and levodopa) Pregnant women Nursing women Women of childbearing potential who are unwilling to employ adequate contraception Known allergy to SAMe Current use or use within the past 6 months of SAMe Clinically significant acute or chronic progressive or unstable neurologic, psychiatric, hepatic, renal, cardiovascular, respiratory, metabolic, or systemic disease precluding participation in the study History of bipolar disorder or Parkinsonism

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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>The first week of the study is a baseline week where data are being collected but study agent is not being taken. Patients then receive oral s-adenosyl-L-methionine, 400 mg, once daily on days 8-14 and twice daily on days 15-49 in the absence of unacceptable toxicity. | Drug: S-adenosyl-L-methionine disulfate p-toluene-sulfonate<br>* Given orally<br>* Other names: SAMe disulfate p-toluene-sulfonate;Other: questionnaire administration<br>* Ancillary studies<br>Procedure: quality-of-life assessment<br>* Ancillary studies<br>* Other names: quality of life assessment;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Baseline in Average Hot Flash Activity (Score and Frequency) | Hot flash score was defined as the number of mild hot flashes for the week plus two times the number of moderate hot flashes plus three times the number of severe hot flashes plus four times the number of very severe hot flashes. Hot flash frequency was defined as the average number of hot flashes per day for each week. Week 7 percent of baseline was calculated. The reduction in hot flash score and frequency can be calculated by subtracting the week 7 percent of baseline from 100 percent. | From baseline to week 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 7 for the Side Effect Questionnaire (SEQ) | The side effect questionnaire (SEQ) consists of 15 items on a scale of 0 to 10 with 10 represents worse symptoms. Each item were reported as individual scores with all scores transposed to a 0-100 point percentage scale where 100 is the best quality of life (QOL) scores. Change from baseline to week 7 scores was calculated by subtracting the baseline scores from the scores at week 7. The positive change in scores indicates an improvement in QOL and negative change in scores indicates a decline in QOL. | Baseline and Week 7 | 
| Change From Baseline to Week 7 for the Profile of Mood States (POMS) | The Profile of Mood States (POMS) consists of 30 items on scale of 0 to 4 (0=not at all, 1=a little, 2=moderately, 3=quite a bit and 4=extremely). The POMS was scored according to its specific scoring algorithm resulting in a total score and six subscale scores (anger/hostility, confusion/bewilderment, depression/dejection, fatigue/inertia, tension/anxiety, and vigor/activity). All scores were transposed to a 0-100 point percentage scale where 100 is the best quality of life (QOL) scores. Change from baseline to week 7 scores was calculated by subtracting the baseline scores from the scores at week 7. The positive change in scores indicates an improvement in QOL and negative change in scores indicates a decline in QOL. | Baseline and Week 7 | 
| Change From Baseline to Week 7 for the Hot Flash Related Daily Interference Scale (HFRDIS) | The Hot Flash Related Daily Interference Scale (HFRDIS) consists of 10 items on scale of 0 to 10 with 0 represents do not interfere and 10 represents completely interferes. An average of the scores of the 10 individual items was calculated for the HFRDIS total score. Each individual item were reported as individual scores. All scores were transposed to a 0-100 point percentage scale where 100 is the best quality of life (QOL) scores. Change from baseline to week 7 scores was calculated by subtracting the baseline scores from the scores at week 7. The positive change in scores indicates an improvement in QOL and negative change in scores indicates a decline in QOL. | Baseline and Week 7 | 
| Number of Patients Who Reported Grade 3 Adverse Events | Adverse events were assessed per NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. | Week 1 to Week 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hot flashes, dietary supplements, symptom management