Phase III Double-Blind, Randomized, Placebo-Controlled Crossover Trial of Black Cohosh in the Management of Hot Flashes: NCCTG Trial N01CC1

Purpose Hot flashes can cause significant morbidity in postmenopausal women undergoing or finished with breast cancer treatment. Black cohosh has been used to treat hot flashes, but definitive clinical data about efficacy have been equivocal. Methods A double-blind, randomized, cross-over clinical trial with two 4-week periods, was used to study the efficacy of black cohosh (1 capsule, Cimicifuga racemosa 20 mg BID) for the treatment of hot flashes in women. Participants kept a daily hot flash diary during a baseline week and then during two 4-week crossover treatment periods. Hot flash scores were measured by assigning points (1 to 4 for mild to very severe) to each hot flash based on severity and then adding the points for a given time period. Results Between October 31, 2003, to March 4, 2004, 132 patients were randomly assigned. Toxicity was minimal and not different by treatment group. Patients receiving black cohosh reported a mean decrease in hot flash score of 20% (comparing the fourth treatment week to the baseline week) compared with a 27% decrease for patients on placebo (P = .53). Mean hot flash frequency was reduced 17% on black cohosh and 26% on placebo (P = .36). Patient treatment preferences were measured after completion of both treatment periods by ascertaining which treatment period, if any, the patient preferred. Thirty-four percent of patients preferred the black cohosh treatment, 38% preferred the placebo, and 28% did not prefer either treatment. Conclusion This trial failed to provide any evidence that black cohosh reduced hot flashes more than the placebo.

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Phase III, Placebo-Controlled Trial of Three Doses of Citalopram for the Treatment of Hot Flashes: NCCTG Trial N05C9

Journal of Clinical Oncology ◽

10.1200/jco.2009.26.6379 ◽

2010 ◽

Vol 28 (20) ◽

pp. 3278-3283 ◽

Cited By ~ 69

Author(s):

Debra L. Barton ◽

Beth I. LaVasseur ◽

Jeff A. Sloan ◽

Allen N. Stawis ◽

Kathleen A. Flynn ◽

...

Keyword(s):

Controlled Trial ◽

Hot Flashes ◽

Study Data ◽

Phase Iii ◽

Double Blind Trial ◽

Double Blind ◽

Hot Flash ◽

Rigorous Evaluation ◽

Secondary Outcomes

Purpose Up to 75% of women experience hot flashes, which can negatively impact quality of life. As hot flash physiology is not definitively understood, it cannot be assumed that effective agents represent class effects. Therefore, there is a continued need for rigorous evaluation to identify effective nonhormonal options for hot flash relief. Methods A randomized, double-blind trial evaluated citalopram at target doses of 10, 20, or 30 mg/d versus placebo for 6 weeks. Postmenopausal women with at least 14 bothersome hot flashes per week recorded hot flashes for 7 days before starting treatment and were then titrated to their target doses. The primary end point was the change from baseline to 6 weeks in hot flash score. Results Two hundred fifty-four women were randomly assigned onto this study. Data for hot flash scores and frequencies showed significant improvement in hot flashes with citalopram over placebo, with no significant differences among doses. Reductions in mean hot flash scores were 2.0 (23%), 7.0 (49%), 7.7 (50%), and 10.7 (55%) for placebo and 10, 20, and 30 mg of citalopram, respectively (P ≤ .002). Improvement in secondary outcomes, such as the Hot Flash Related Daily Interference Scale, was statistically superior in the 20-mg arm. Citalopram was well-tolerated, with no significant negative adverse effects. Conclusion Citalopram is an effective, well-tolerated agent in managing hot flashes. There does not appear to be a significant dose response above 10 mg/d, but broader helpful effects of the agent appear to be more evident at 20 mg/d.

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Phase III, Randomized, Double-Blind, Placebo-Controlled Evaluation of Pregabalin for Alleviating Hot Flashes, N07C1

Journal of Clinical Oncology ◽

10.1200/jco.2009.24.5647 ◽

2010 ◽

Vol 28 (4) ◽

pp. 641-647 ◽

Cited By ~ 74

Author(s):

Charles L. Loprinzi ◽

Rui Qin ◽

Ernie P. Baclueva ◽

Kathleen A. Flynn ◽

Kendrith M. Rowland ◽

...

Keyword(s):

Randomized Trial ◽

Trial Design ◽

Hot Flashes ◽

Phase Iii ◽

Target Dose ◽

Double Blind ◽

Hot Flash ◽

Double Blind Placebo ◽

Current Trial ◽

Controlled Evaluation

Purpose Hot flashes are a common problem for which effective and safe treatments are needed. The current trial was conducted on the basis of preliminary promising data that pregabalin decreased hot flashes. Patients and Methods A double-blind, placebo-controlled, randomized trial design was used to compare pregabalin at target doses of 75 mg twice daily and 150 mg twice daily with a placebo. Hot flash frequencies and scores (frequency times mean severity) were recorded daily during a baseline week and for six treatment weeks. The primary end point for this study was the change-from-baseline hot flash score during treatment week 6 between the 150 mg twice daily target pregabalin treatment and placebo. Nonparametric Wilcoxon rank sum tests, two-sample t tests, and χ2 tests were used to compare the primary and secondary hot flash efficacy end points between pregabalin treatments and placebo. Results Hot flash score changes available for 163 patients during the sixth treatment week compared with a baseline week decreased by 50%, 65%, and 71% in the placebo, and target 75 mg twice daily and 150 mg twice daily pregabalin arms, respectively (P = .009 and P = .007, comparing respective pregabalin arms to the placebo arm). While some toxicities were significantly more common in the pregabalin arms, being more evident with the higher dose, pregabalin was generally well tolerated by most patients. Conclusion Pregabalin decreases hot flashes and is reasonably well tolerated. A target dose of 75 mg twice daily is recommended. Its effects appear to be roughly comparable to what has been reported with gabapentin and with some newer antidepressants.

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Transdermal clonidine for ameliorating tamoxifen-induced hot flashes.

Journal of Clinical Oncology ◽

10.1200/jco.1994.12.1.155 ◽

1994 ◽

Vol 12 (1) ◽

pp. 155-158 ◽

Cited By ~ 212

Author(s):

R M Goldberg ◽

C L Loprinzi ◽

J R O'Fallon ◽

M H Veeder ◽

A W Miser ◽

...

Keyword(s):

Breast Cancer ◽

Prospective Study ◽

Hot Flashes ◽

Estrogen Therapy ◽

Crossover Design ◽

Double Blind ◽

Hot Flash ◽

Mouth Dryness ◽

History Of ◽

Protocol Study

PURPOSE To determine the efficacy of transdermal clonidine for alleviating tamoxifen-induced hot flashes in women with a history of breast cancer. PATIENTS AND METHODS A randomized, double-blind, crossover design was used in this prospective study. Women with a history of breast cancer who were receiving tamoxifen and suffering from hot flashes were potentially eligible for this protocol study. RESULTS Clonidine did reduce hot-flash frequency to a degree that was statistically impressive (P < .0001), but clinically moderate (20% reduction from baseline). It also decreased hot-flash severity (P = .02, 10% reduction from baseline). Clonidine was related to increased mouth dryness (P < .001), constipation (P < .02), itchiness under the patch (P < .01), and drowsiness (P < .05). CONCLUSION Better means are needed to alleviate hot flashes among patients in whom estrogen therapy is contraindicated.

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A double-blind, randomized cross-over trial of venlafaxine versus clonidine to treat hot flashes in breast cancer patients

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.9083 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 9083-9083

Author(s):

C. Mom ◽

C. Buijs ◽

P. H. Willemse ◽

H. Boezen ◽

J. Maurer ◽

...

Keyword(s):

Breast Cancer ◽

Side Effects ◽

Cancer Patients ◽

Hot Flashes ◽

Breast Cancer Patients ◽

Double Blind ◽

Hot Flash ◽

History Of ◽

Loss Of Appetite ◽

To Receive

9083 Background: Breast cancer patients who become postmenopausal due to their treatment can experience more frequent and severe hot flashes than healthy postmenopausal women. Estrogens are considered to be contra-indicated. Venlafaxine and clonidine are both used to alleviate hot flashes, with different side effects. This study compared side effects, efficacy and patient preference. Methods: In a double-blind, cross-over study women <60 years, with a history of breast cancer, and experiencing at least 14 hot flashes/week were randomized to receive venlafaxine 75 mg od (and placebo bid) for 8 weeks, followed by a 2 week wash-out period, and 8 weeks of clonidine 0.025 mg bid (and placebo od) or vice versa. Hot flash frequency and hot flash score (frequency × severity) were recorded in a diary and side effects were scored using a questionnaire during the 2nd and 8th week of both treatment periods, and these were compared to a baseline week. Results: Sixty patients were randomized to start with venlafaxine (n=30) and clonidine (n=30), 40 completed both treatment periods. Premature treatment discontinuation occurred in 15/59 patients during venlafaxine and in 5/53 during clonidine due to side effects (p<0.05). The main side effects of venlafaxine were nausea and headache, and of clonidine dry mouth. In the 8th week of treatment women reported more loss of appetite (24% vs 4%; p=0.03) and improved sleeping (55% vs 75%; p=0.03) with venlafaxine. A =50% reduction in hot flash score was found in 21 (49%) and 26 (55%) of the patients with venlafaxine and clonidine respectively (ns). The decrease in hot flash score was most marked in the first treatment period. At study completion 20 (33%) of the patients chose to continue clonidine, and 17 (29%) preferred venlafaxine (ns), whereas 23 (38%) declined further treatment. Conclusions: Venlafaxine and clonidine are both moderately and equally effective in the reduction of hot flashes. Side effects are the main reason for discontinuation, occurring more often during treatment with venlafaxine. No significant financial relationships to disclose.

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The evaluation of flaxseed for hot flashes: Results of a randomized, controlled trial, NCCTG study N08C7.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.18_suppl.cra9015 ◽

2011 ◽

Vol 29 (18_suppl) ◽

pp. CRA9015-CRA9015 ◽

Cited By ~ 1

Author(s):

S. Pruthi ◽

R. Qin ◽

S. A. Terstriep ◽

H. Liu ◽

C. L. Loprinzi ◽

...

Keyword(s):

Placebo Group ◽

Side Effects ◽

Controlled Trial ◽

Hot Flashes ◽

Group Versus ◽

Abdominal Distension ◽

Self Report ◽

Phase Iii ◽

Common Symptom ◽

Hot Flash

CRA9015 Background: Hot flashes are a common symptom during the menopause transition or following breast cancer treatment that can negatively impact the quality of life for many women. Preliminary data have suggested that flaxseed, a rich source of dietary lignans, may be a potentially effective treatment for hot flashes. Methods: A phase III randomized, placebo controlled trial was conducted to evaluate the efficacy of flaxseed in reducing hot flashes. Postmenopausal women were randomly assigned to a flaxseed bar (providing 410 mg of lignans) for 6 weeks vs a placebo bar. Participants completed daily prospective, self report hot flash diaries during the baseline week and then began eating one study bar per day for 6 weeks, while continuing to record their daily hot flashes. The intra-patient difference in hot flash activity between baseline and the last treatment week was the primary endpoint. Side effects of the bars were evaluated through self report and CTC assessment. Results: Between October and December 2009, 188 women were enrolled onto this trial. Mean hot flash scores were reduced by 4.9 units in the flaxseed group and 3.5 in the placebo group (p=0.29). In both groups, a little over a third of the women received a 50% reduction in their hot flash scores. Only one side effect was significantly different between groups, that being grade 1 pruritis, which was more common (7%) in the placebo group versus 1% in the flaxseed group. Both groups reported increased abdominal distension, flatulence, diarrhea and nausea. Adherence and ability to detect treatment assignment did not differ between groups. Conclusions: The results of this trial do not support the use of 410 mg of flaxseed lignans for the reduction of hot flashes. The gastrointestinal side effects seen in both groups were likely due to the fiber content in the flaxseed and placebo bars.

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Fampridine and Acetazolamide in EA2 and Related Familial EA: A Prospective Randomized Placebo-controlled Trial

Neurology Clinical Practice ◽

10.1212/cpj.0000000000001017 ◽

2020 ◽

pp. 10.1212/CPJ.0000000000001017

Author(s):

Carolin Muth ◽

Julian Teufel ◽

Ludger Schöls ◽

Matthis Synofzik ◽

Christiana Franke ◽

...

Keyword(s):

Crossover Trial ◽

Controlled Trial ◽

Random Sequence ◽

Positive Family History ◽

Phase Iii ◽

Prolonged Release ◽

Taste Disturbance ◽

Double Blind ◽

Episodic Ataxia Type 2 ◽

Gastrointestinal Complaints

AbstractObjectiveWe determine the efficacy and safety of the treatment with prolonged-release 4-aminopyridine (fampridine) and acetazolamide for patients with episodic ataxia type 2 (EA2). Therefore, 30 patients with EA2 were treated with a random sequence of fampridine, acetazolamide, and placebo in a three-period crossover trial.MethodsA total of 30 patients with EA2 (eight female; aged 20-71 years; 18 genetically confirmed, four with a positive family history, eight with the clinical diagnosis) were enrolled in this phase III, randomised, double-blind, placebo-controlled, three-period crossover trial. Each period lasted 12 weeks with a four-week washout-period. Each patient received a random sequence of 20 mg/d fampridine, 750 mg/d acetazolamide, and placebo. The primary endpoint was the number of attacks during the last 30 days within the 12-week treatment-period. Participants, caregivers, and those assessing the outcomes were blinded to the intervention.ResultsCompared to placebo, fampridine reduced the number of attacks to 63% (95% CI 54% - 74%) and acetazolamide to 52% (95% CI 46% - 60%). A total of 39 (26.5%) adverse events were observed under treatment with fampridine (mostly tingling paraesthesia, and fatigue), 66 (44.9%) happened under acetazolamide (mostly taste disturbance, gastrointestinal complaints), and 42 (28.6%) under placebo (mostly gastrointestinal complaints).ConclusionBoth fampridine and acetazolamide significantly reduce the number of attacks in patients with EA2 and related EA in comparison to placebo. Fampridine 10 mg twice daily had fewer side effects than acetazolamide 250 mg three times daily.

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Newer Antidepressants and Gabapentin for Hot Flashes: An Individual Patient Pooled Analysis

Journal of Clinical Oncology ◽

10.1200/jco.2008.19.6253 ◽

2009 ◽

Vol 27 (17) ◽

pp. 2831-2837 ◽

Cited By ~ 106

Author(s):

Charles L. Loprinzi ◽

Jeff Sloan ◽

Vered Stearns ◽

Rebecca Slack ◽

Malini Iyengar ◽

...

Keyword(s):

Treatment Options ◽

Hot Flashes ◽

Clinical Problem ◽

Pooled Analysis ◽

Double Blind ◽

Hot Flash ◽

Study Results ◽

Study Heterogeneity ◽

Study Characteristics ◽

Major Clinical Problem

Purpose Nonhormonal treatment options have been investigated as treatments for hot flashes, a major clinical problem in many women. Starting in 2000, a series of 10 individual double-blind placebo-controlled studies has evaluated newer antidepressants and gabapentin for treating hot flashes. This current project was developed to conduct an individual patient pooled analysis of the data from these published clinical trials. Patients and Methods Individual patient data were collected from the various study investigators who published their study results between 2000 and 2007. Between-study heterogeneity for study characteristics and patient populations was tested via χ2 tests before a pooled analysis. The primary end point, the change in hot flash activity from baseline to week 4, for each agent was calculated via both weighted and unweighted approaches, using the size of the study as the weight. Basic summary statistics were produced for hot flash score and frequency using the following three statistics: raw change, percent reduction, and whether or not a 50% reduction was achieved. Results This study included seven trials of newer antidepressants and three trials of gabapentin. The optimal doses (defined by individual study results) of the newer antidepressants paroxetine, venlafaxine, fluoxetine, and sertraline decreased hot flash scores by 41%, 33%, 13%, and 3% to 18% compared with the corresponding placebo arms, respectively. The three gabapentin trials decreased hot flashes by 35% to 38% compared with the corresponding placebo arms. Conclusion Some newer antidepressants and gabapentin, within 4 weeks of therapy initiation, decrease hot flashes more than placebo.

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Internet based double-blind cross-over clinical trial to test efficacy of high dose isoflavone soy in controlling breast cancer survivor hot flashes

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.636 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 636-636 ◽

Cited By ~ 1

Author(s):

W. C. Dooley ◽

C. Hendricks ◽

Y. Gusev ◽

L. Shockney

Keyword(s):

Breast Cancer ◽

Cancer Survivor ◽

Breast Cancer Survivor ◽

Breast Cancer Survivors ◽

Controlled Trial ◽

Hot Flashes ◽

Time Of Day ◽

High Dose ◽

Double Blind ◽

Hot Flash

636 Background: Severe hot flashes are common after completion of allopathic breast cancer treatment. Hot flashes are rare in the Orient where high isoflavone soy diets are common. Methods: We enrolled breast cancer survivors experiencing hot flashes after the completion of surgery, radiation and chemotherapy into a 16 week double blind cross-over casein placebo controlled trial of a 160 mg isoflavone soy dietary supplement. Hot flash frequency, severity, and time of day, exercise time and patient journaling was recorded by an internet diary placed on a HIPPA compliant server with password access. Results: Of 168 patients enrolled, 117 actually participated in taking supplementation and completing internet diaries giving adequate data for analysis. Of this group 13 patients dropped out of study for failure to finish all dietary supplements throughout the study period. The hot flash data during the last 4 weeks on each supplement was compared to determine benefit. There was no statistical difference in hot flash frequency, intensity or duration between either supplement independent of exercise level. Interestingly, 82% of patients reported a decrease in hot flashes in the first 4 weeks of study independent of which supplement they were randomized to receive. The journal entries report during this “induction” period that the majority of patients had identified emotional or dietary or other triggers for their hot flashes. The avoidance of the triggers seemed to substantially reduce their reported menopausal symptoms. Conclusions: High dose soy isoflavone dietary supplementation is ineffective in reducing breast cancer survivor hot flashes. Journaling may have a benefit in allowing survivors to find their individual triggers for the most severe hot flashes. Internet patient data entry provides a unique and highly compliant tool for obtaining direct patient reporting in survivorship clinical trials. [Table: see text]

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