Healthy, no Evidence of Disease, Hot Flashes
Conditions
Keywords
Hot flashes, dietary supplements, symptom management
Brief summary
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
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.
Interventions
Given orally
OTHERquestionnaire administration
Ancillary studies
PROCEDUREquality-of-life assessment
Ancillary studies
Sponsors
Mayo Clinic
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Baseline in Average Hot Flash Activity (Score and Frequency) | From baseline to week 7 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 7 for the Side Effect Questionnaire (SEQ) | Baseline and Week 7 | 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. |
| Change From Baseline to Week 7 for the Profile of Mood States (POMS) | Baseline and Week 7 | 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. |
| Change From Baseline to Week 7 for the Hot Flash Related Daily Interference Scale (HFRDIS) | Baseline and Week 7 | 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. |
| Number of Patients Who Reported Grade 3 Adverse Events | Week 1 to Week 7 | Adverse events were assessed per NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. |
Countries
United States
Participant flow
Recruitment details
Forty-five (45) subjects were recruited between October 2010 and January 2012 at Mayo Clinic.
Pre-assignment details
Two subjects were ineligible and excluded from all analyses except adverse events summary.
Participants by arm
| Arm | Count |
|---|---|
| SAMe 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. | 43 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Refused Further Treatment | 5 |
Baseline characteristics
| Characteristic | SAMe |
|---|---|
| Age, Continuous | 55.1 years STANDARD_DEVIATION 6.5 |
| Aromatase Inhibitor Therapy No | 38 Participants |
| Aromatase Inhibitor Therapy Yes | 5 Participants |
| Average Hot Flashes per Day >=10 | 19 Participants |
| Average Hot Flashes per Day 2-3 | 3 Participants |
| Average Hot Flashes per Day 4-9 | 21 Participants |
| Breast Cancer History No | 25 Participants |
| Breast Cancer History Yes | 18 Participants |
| Duration of Flash Symptoms (months) <9 months | 5 Participants |
| Duration of Flash Symptoms (months) >=9 months | 38 Participants |
| Raloxifene Therapy No | 43 Participants |
| Raloxifene Therapy Yes | 0 Participants |
| Region of Enrollment United States | 43 participants |
| Sex: Female, Male Female | 43 Participants |
| Sex: Female, Male Male | 0 Participants |
| Tamoxifen Therapy No | 35 Participants |
| Tamoxifen Therapy Yes | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 41 / 45 |
| serious Total, serious adverse events | 2 / 45 |
Outcome results
Primary
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.
Time frame: From baseline to week 7
Population: Analysis population includes only the subjects who have completed the quality of life self-assessment questionnaire.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| SAMe | Percent of Baseline in Average Hot Flash Activity (Score and Frequency) | Week 7 percent of baseline for Hot Flash Score | 64.6 Percent of baseline |
| SAMe | Percent of Baseline in Average Hot Flash Activity (Score and Frequency) | Week 7 percent of baseline for Hot flash frequency | 67.4 Percent of baseline |
Comparison: To determine whether any reduction in hot flash score is beyond what is expected with a placebo (20-25%). Reference: Sloan JA, et al. Methodologic lessons learned from hot flash studies. J Clin Oncol. Dec 1 2001;19(23):4280-4290.p-value: 0.0903t-test, 1 sided
Comparison: To determine whether any reduction in hot flash frequency is beyond what is expected with a placebo (20-25%). Reference: Sloan JA, et al. Methodologic lessons learned from hot flash studies. J Clin Oncol. Dec 1 2001;19(23):4280-4290.p-value: 0.1553t-test, 1 sided
Secondary
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.
Time frame: Baseline and Week 7
Population: Includes all participants who initiated the study treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAMe | Change From Baseline to Week 7 for the Hot Flash Related Daily Interference Scale (HFRDIS) | HFRDIS total | 8.6 score on a scale | Standard Deviation 14.4 |
| SAMe | Change From Baseline to Week 7 for the Hot Flash Related Daily Interference Scale (HFRDIS) | Mood | 13.9 score on a scale | Standard Deviation 16.3 |
| SAMe | Change From Baseline to Week 7 for the Hot Flash Related Daily Interference Scale (HFRDIS) | Sleep | 21.6 score on a scale | Standard Deviation 30 |
| SAMe | Change From Baseline to Week 7 for the Hot Flash Related Daily Interference Scale (HFRDIS) | Concentration | 12.8 score on a scale | Standard Deviation 21.3 |
| SAMe | Change From Baseline to Week 7 for the Hot Flash Related Daily Interference Scale (HFRDIS) | Overall QOL | 7.8 score on a scale | Standard Deviation 21.1 |
| SAMe | Change From Baseline to Week 7 for the Hot Flash Related Daily Interference Scale (HFRDIS) | Enjoyment of life | 5.9 score on a scale | Standard Deviation 17.4 |
| SAMe | Change From Baseline to Week 7 for the Hot Flash Related Daily Interference Scale (HFRDIS) | Social activities | 5.3 score on a scale | Standard Deviation 17 |
| SAMe | Change From Baseline to Week 7 for the Hot Flash Related Daily Interference Scale (HFRDIS) | Leisure activities | 4.7 score on a scale | Standard Deviation 15.2 |
| SAMe | Change From Baseline to Week 7 for the Hot Flash Related Daily Interference Scale (HFRDIS) | Work | 4.4 score on a scale | Standard Deviation 19.3 |
| SAMe | Change From Baseline to Week 7 for the Hot Flash Related Daily Interference Scale (HFRDIS) | Relationships with others | 3.4 score on a scale | Standard Deviation 15.6 |
| SAMe | Change From Baseline to Week 7 for the Hot Flash Related Daily Interference Scale (HFRDIS) | Sexuality | 2.8 score on a scale | Standard Deviation 23.7 |
Secondary
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.
Time frame: Baseline and Week 7
Population: Includes all participants who initiated the study treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAMe | Change From Baseline to Week 7 for the Profile of Mood States (POMS) | POMS total | 3.0 score on a scale | Standard Deviation 7.8 |
| SAMe | Change From Baseline to Week 7 for the Profile of Mood States (POMS) | Fatigue/inertia | 10.9 score on a scale | Standard Deviation 18.7 |
| SAMe | Change From Baseline to Week 7 for the Profile of Mood States (POMS) | Anger/hostility | 2.8 score on a scale | Standard Deviation 10.1 |
| SAMe | Change From Baseline to Week 7 for the Profile of Mood States (POMS) | Tension/anxiety | 2.3 score on a scale | Standard Deviation 10.8 |
| SAMe | Change From Baseline to Week 7 for the Profile of Mood States (POMS) | Confusion/bewilderment | 1.2 score on a scale | Standard Deviation 10.6 |
| SAMe | Change From Baseline to Week 7 for the Profile of Mood States (POMS) | Depression/dejection | 0.7 score on a scale | Standard Deviation 8.8 |
| SAMe | Change From Baseline to Week 7 for the Profile of Mood States (POMS) | Vigor/activity | 0.5 score on a scale | Standard Deviation 13.9 |
Secondary
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.
Time frame: Baseline and Week 7
Population: Includes all participants who initiated the study treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAMe | Change From Baseline to Week 7 for the Side Effect Questionnaire (SEQ) | Abnormal sweating | 25 score on a scale | Standard Deviation 34.5 |
| SAMe | Change From Baseline to Week 7 for the Side Effect Questionnaire (SEQ) | Trouble sleeping | 17.5 score on a scale | Standard Deviation 30.7 |
| SAMe | Change From Baseline to Week 7 for the Side Effect Questionnaire (SEQ) | Fatigue | 11.7 score on a scale | Standard Deviation 25.2 |
| SAMe | Change From Baseline to Week 7 for the Side Effect Questionnaire (SEQ) | Muscle or joint aches/pain | 10 score on a scale | Standard Deviation 20.6 |
| SAMe | Change From Baseline to Week 7 for the Side Effect Questionnaire (SEQ) | Trouble concentrating | 7.5 score on a scale | Standard Deviation 20.2 |
| SAMe | Change From Baseline to Week 7 for the Side Effect Questionnaire (SEQ) | Swelling of hands/feet | 2.8 score on a scale | Standard Deviation 18.9 |
| SAMe | Change From Baseline to Week 7 for the Side Effect Questionnaire (SEQ) | Anxiousness | 2.8 score on a scale | Standard Deviation 16.7 |
| SAMe | Change From Baseline to Week 7 for the Side Effect Questionnaire (SEQ) | Constipation | 2.5 score on a scale | Standard Deviation 25 |
| SAMe | Change From Baseline to Week 7 for the Side Effect Questionnaire (SEQ) | Diarrhea | 1.4 score on a scale | Standard Deviation 18.3 |
| SAMe | Change From Baseline to Week 7 for the Side Effect Questionnaire (SEQ) | Headache | 0 score on a scale | Standard Deviation 16 |
| SAMe | Change From Baseline to Week 7 for the Side Effect Questionnaire (SEQ) | Nausea | -1.4 score on a scale | Standard Deviation 18.1 |
| SAMe | Change From Baseline to Week 7 for the Side Effect Questionnaire (SEQ) | Lack of coordination | -3.8 score on a scale | Standard Deviation 14.8 |
| SAMe | Change From Baseline to Week 7 for the Side Effect Questionnaire (SEQ) | Appetite | -4.1 score on a scale | Standard Deviation 17.8 |
| SAMe | Change From Baseline to Week 7 for the Side Effect Questionnaire (SEQ) | Dry mouth | -4.1 score on a scale | Standard Deviation 22.4 |
| SAMe | Change From Baseline to Week 7 for the Side Effect Questionnaire (SEQ) | Sleepiness | -15.5 score on a scale | Standard Deviation 25.6 |
Secondary
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.
Time frame: Week 1 to Week 7
Population: All participants who enrolled to the trial.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SAMe | Number of Patients Who Reported Grade 3 Adverse Events | Insomnia | 2 Participants |
| SAMe | Number of Patients Who Reported Grade 3 Adverse Events | Neoplasms: benign, malignant, unspecified | 1 Participants |