scholarly journals SAT-001 Clinically Meaningful Effects of E2/P4 Oral Capsule in Treating Vasomotor Symptoms

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Ginger Constantine ◽  
Shelli Graham ◽  
Dennis A Revicki ◽  
Risa Kagan ◽  
Sebastian Mirkin
Keyword(s):  
Controlled Trial ◽  
Clinical Importance ◽  
Vasomotor Symptoms ◽  
Life Questionnaire ◽  
Double Blind ◽  
Exact Test ◽  
Menopausal Women ◽  
Patient Reported ◽  
Hormonal Therapies

Abstract Hormonal therapies effectively reduce the frequency and severity of vasomotor symptoms (VMS) in menopausal women; however, whether the effect is clinically meaningful to women is typically not determined. Oral estradiol/progesterone (E2/P4; mg/mg) 1/100 and 0.5/100 significantly improved moderate to severe VMS versus placebo at weeks 4 and 12. The objective of these analyses was to determine the clinical importance (meaningfulness) of E2/P4 treatment versus placebo in menopausal women. REPLENISH, a phase 3, randomized, double-blind, placebo-controlled trial, evaluated the safety and efficacy of E2/P4 oral capsules in symptomatic, postmenopausal women with a uterus. Clinically meaningful reductions in weekly VMS frequency were determined using 3 patient-reported outcomes as anchors (VMS severity score, clinical global impression [CGI], and question 1 from the vasomotor domain of the menopause-specific quality of life questionnaire). The proportion of women who had a clinically important response with 0.5/100 was compared with placebo using the Fisher’s exact test. Spearman correlations were also performed across the 3 anchors. Clinically meaningful reductions in weekly VMS frequency ranged from 32 to 43 at week 4, and from 32 to 48 at week 12. Significantly more responders were observed with 0.5/100 than with placebo for all 3 anchors at both weeks 4 (all, P<0.05) and 12 (all, P≤0.002). All 3 anchors were correlated, supporting their acceptability as appropriate anchors. Treatment with E2/P4 0.5/100 provided consistent clinically meaningful improvements in the weekly frequency of moderate to severe VMS in menopausal women, similar to what has been observed with the CGI-anchor for E2/P4 1/100.

scholarly journals OR11-03 NT-814, a Non-Hormonal Dual Neurokinin 1,3 Receptor Antagonist Markedly Improves Vasomotor Symptoms in Post-Menopausal Women; Results of a Randomised, Double-Blind, Placebo-Controlled, Dose-Finding Study (SWITCH-1)

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
James Simon ◽  
Richard A Anderson ◽  
Elizabeth Ballantyne ◽  
Hadine Joffe ◽  
Mary Kerr ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Dose Finding ◽  
Vasomotor Symptoms ◽  
Phase 3 ◽  
Double Blind ◽  
Once Daily ◽  
Double Blind Placebo ◽  
Menopausal Women ◽  
Post Menopausal

Abstract Introduction: Vasomotor symptoms (VMS), caused by declining estrogen in menopausal women, are common and debilitating. Hormone therapy is effective in many women but carries risks and may be contraindicated. Biological and clinical evidence shows a modulatory role for neurokinin (NK) receptor antagonists acting primarily via hypothalamic KNDy (kisspeptin, NK, dynorphin) neurons on VMS. NT-814 is an oral non-hormonal dual NK1,3 receptor antagonist which has previously been shown to cause rapid and marked improvements in VMS in post-menopausal women. This Phase-2b trial (SWITCH-1) was undertaken to further evaluate efficacy and safety and to establish the optimum dose(s) for Phase 3 studies. Methods: SWITCH-1 was a double-blind, placebo-controlled, adaptive-randomization, dose-finding trial in 199 post-menopausal women. After a 2-week single-blind placebo run-in to establish symptom stability, women (40 to 65 years) with ≥7 moderate and/or severe VMS per day at baseline were randomized to 12 weeks of once daily treatment with placebo or one of 4 doses of NT-814: 40 mg, 80 mg, 120 mg, 160 mg. Subjects recorded the frequency and severity of VMS in electronic diaries twice daily throughout the study. Patient-reported measures of quality-of-life, sleep and mood were collected periodically. Adverse events (AEs) were recorded at each clinic visit. Results: VMS frequency was reduced in all treatment groups, including placebo. VMS reductions were significantly greater with the 2 higher NT-814 doses at most time-points, as early as the first week of treatment. Least squares mean reductions from baseline in moderate/severe VMS per day at week 4 were: placebo, 2.7; 40 mg, 4.3 (p=0.161 vs placebo); 80 mg, 4.1 (p=0.326); 120 mg, 6.7 (p<0.0001); 160 mg, 5.5 (p=0.007). In week 12 the reductions were: placebo, 4.7; 40 mg, 6.5 (p=0.185); 80 mg, 5.6 (p=0.599); 120 mg, 7.8 (p=0.009); 160 mg, 6.6 (p=0.109). At the 160 mg dose the median reduction in week 12 was significantly greater than placebo (6.9 vs 4.4, p=0.0023), indicating an effect of high outliers on the mean. Average HF severity was also improved in a dose-related manner, with greater reductions compared to placebo with the 2 higher NT-814 doses. Improvements in HF were accompanied by statistically significant benefits on sleep (assessed using the Insomnia Severity Index and Pittsburgh Sleep Quality Index), mood (measured using the Beck Depression Inventory), and all four domains of the MenQoL menopause-specific quality-of-life instrument. NT-814 was well-tolerated; most AEs were mild or moderate and there were no serious AEs related to treatment. Conclusions: NT-814, a once daily non-hormonal NK antagonist, at doses of 120 & 160 mg reduced the frequency and severity of VMS and significantly improved quality of life, mood and sleep, in postmenopausal women. NT-814 was well tolerated, with a safety profile that supports further evaluation in Phase 3 trials.

The Effect of Aromatherapy on Sleep and Quality of Life in Menopausal Women with Sleeping Problems: A Non-Randomized, Placebo-Controlled Trial

2020 ◽  
Vol 27 (6) ◽  
pp. 421-430
Author(s):  
Meryem Gürler ◽  
Aynur Kızılırmak ◽  
Mürüvvet Baser
Keyword(s):  
Quality Of Life ◽  
Placebo Group ◽  
Sleep Quality ◽  
Controlled Trial ◽  
Intervention Group ◽  
Placebo Control ◽  
Life Questionnaire ◽  
Menopausal Women ◽  
Sleeping Problems

<b><i>Introduction:</i></b> Menopause is the termination of menstruation and fertility. Women commonly experience sleeping problems during the menopausal period. Aromatherapy is among the complementary therapies used to remedy sleeping problems. <b><i>Methods:</i></b>This study aims to investigate the effects of lavender oil on sleep and quality of life of menopausal women through steam inhalation. This study was quasi-experimental with pre-test/post-test placebo control groups. It was conducted with 57 women, 27 of whom were subject to aromatherapy and 30 to a placebo. Data were collected using the Questionnaire Form, the Pittsburgh Sleep Quality Index (PSQI) and the Menopause-Specific Quality of Life Questionnaire (MENQOL). <b><i>Results:</i></b> For the intervention group, the PSQI median scores after the administration of aromatherapy were found to be significantly lower than those before the administration (<i>p</i> &#x3c; 0.001) and those of the placebo group (<i>p</i> &#x3c; 0.001). Similarly, for the intervention group, the total median MENQOL scores after the administration of the aromatherapy were found to be significantly lower than the scores prior to the administration (<i>p</i> &#x3c; 0.001) as well as the scores of the placebo group (<i>p</i> &#x3c; 0.001). <b><i>Conclusion:</i></b> It was found that aromatherapy involving lavender-scented steam inhalation increased sleep quality and quality of life in women with sleep deprivation problems during menopause.

scholarly journals Comparative Efficacy of Zolpidem and Nigella Sativa in Treatment of Sleep Disorder and Vasomotor Symptoms in Menopausal Women of Women’s General Hospital

2020 ◽  
Author(s):  
Mojgan Asadi ◽  
Fatemeh Molavi ◽  
Mostafa Qorbani ◽  
Fatemeh Davari Tanha
Keyword(s):  
Sleep Quality ◽  
Postmenopausal Women ◽  
Nigella Sativa ◽  
Controlled Trial ◽  
Hot Flashes ◽  
Vasomotor Symptoms ◽  
Double Blind ◽  
Menopausal Women ◽  
Night Sweats ◽  
Group B

Objective: To evaluate the efficacy of Zolpidem and Nigella sativa compared to placebo in treatment of sleep disturbance in healthy postmenopausal women. Menopause is a period that diagnosed after 12 months of amenorrhea and is characterized by a group of symptoms that include irregular menses; vasomotor and urogenital symptoms. The effects of non-hormonal therapies are being widely researched on menopause symptoms. There has been no study to compare Zolpidem and Nigella sativa versus placebo. Materials and methods: In this double-blind, placebo controlled trial, we compared the effect of Zolpidem with Nigella sativa and placebo in reducing sleep quality in 60 menopausal women. The prior and the later results were compared. We divided the patients into three groups after history taking and physical examination and filling the Pittsburgh questionnaire. Each group received their medication as the following order: Group A: Zolpidem, Group B: Nigella sativa, Group C: placebo. The first group received Zolpidem with the dose of 5 mg for 8 weeks. The second group received Nigella sativa with the dose of 600 mg for 8 weeks. The third group received placebo for 8 weeks. After two months, the Pittsburg questionnaire was filled again. Results: In the nigella sativa group, we had not significant improvement in sleep quality (p =0.07), hot flashes (p =0.15), palpitation (p =0.56) and night sweets (p =0.08).  In zolpidem group, we have seen lack of improvement of hot flashes (p =0.73), and palpitation (p =0.36), which are nonsignificant statistically according to p values, but in zolpidem group, we had significant improvement in sleep quality (p =0.01), and night sweats (p =0.049). Conclusion: It seems that zolpidem has some effect on improving the quality of sleep in postmenopausal women. zolpidem also is good for night sweats. Nigella sativa was not effective in vasomotor symptoms and sleep quality.

scholarly journals Treatment of Menopausal Vasomotor Symptoms With Fezolinetant, a Neurokinin 3 Receptor Antagonist: A Phase 2a Trial

2019 ◽  
Vol 104 (12) ◽  
pp. 5893-5905 ◽  
Author(s):  
Herman Depypere ◽  
Dirk Timmerman ◽  
Gilbert Donders ◽  
Peter Sieprath ◽  
Steven Ramael ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Primary Outcome ◽  
Gastrointestinal Disorder ◽  
Controlled Study ◽  
Vasomotor Symptoms ◽  
Electronic Diary ◽  
Double Blind ◽  
Menopausal Women ◽  
Neurokinin 3 Receptor

Abstract Context The thermoregulatory center in the hypothalamus is stimulated by neurokinin 3 receptor (NK3R) activation and inhibited by estrogen-negative feedback. This balance is disrupted in menopause, producing vasomotor symptoms (VMSs). Objective To evaluate safety and efficacy of the NK3R antagonist fezolinetant in menopausal VMSs. Design Twelve-week, double-blind, randomized, placebo-controlled study. Setting Eight Belgian centers from September 2015 to October 2016. Participants Generally healthy menopausal women aged 40 to 65 years with moderate/severe VMSs. Interventions Subjects were randomized (1:1) to 90 mg of fezolinetant twice daily or placebo for 12 weeks. Main Outcome Measures Subjects captured VMS severity and frequency using an electronic diary. The primary outcome was change from baseline to week 12 in total VMS score with fezolinetant vs placebo. Secondary outcomes included timing of changes in frequency and severity of moderate/severe VMSs and quality-of-life assessments at weeks 4, 8, and 12. Pharmacodynamic and pharmacokinetic effects were assessed, as were safety and tolerability. Results Of 122 subjects screened, 87 were randomized and 80 (92%) completed the study. At week 12, fezolinetant significantly reduced total VMS score vs placebo (−26.5 vs −12.2, P < 0.001) and decreased mean frequency of moderate/severe VMSs by five episodes per day vs placebo. Severity and frequency of moderate/severe VMSs were reduced from the first day of treatment. Improvements were achieved in all quality-of-life measures. Fezolinetant was well tolerated. The most common fezolinetant-related adverse event was gastrointestinal disorder (n = 6). Conclusions Fezolinetant rapidly and significantly reduced moderate/severe VMSs, supporting its potential as an effective nonhormonal treatment option for menopausal women.

Patient-reported diarrhea impact on physical functioning and quality of life in clinical trial data submitted to the U.S. Food and Drug Administration.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19105-e19105
Author(s):  
Ting-Yu Chen ◽  
Bellinda King-Kallimanis ◽  
Lyna Merzoug ◽  
Mallorie Fiero ◽  
Jennifer J Gao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Quality Of Life ◽  
Clinical Trial Data ◽  
Life Questionnaire ◽  
Double Blind ◽  
Patient Reported ◽  
Related Quality ◽  
Cancer Trials ◽  
And Function

e19105 Background: Patient-reported outcomes can provide symptom and function data that complement standard oncology endpoints. Frequently, trials will conclude there was no clinically meaningful detriment to health-related quality of life (HRQL) or function, even when notable toxicity is observed. It is possible that mean change from baseline analyses obscures meaningful change in subgroups experiencing symptomatic toxicity. In this study, we explore how patients’ response to a diarrhea item related to physical function (PF) and HRQL in trials submitted to US FDA. Methods: We analyzed 3 randomized, double-blind breast cancer trials (early to late line metastatic) where diarrhea was a more common AE-symptom in the treatment arm, but there was not a large detriment in the mean change from baseline for HRQL and PF. Trials included the EORTC Quality of Life Questionnaire (QLQ-C30), which captures patient-reported HRQL, symptoms, and functioning. Higher scores (range 0-100) indicate better functioning and HRQL. Symptoms were measured with a 4-point scale; not at all to very much. Descriptive statistics were used to analyze diarrhea, PF, and HRQL over time. Results: Patients reporting very much diarrhea at month 3 had worse PF and HRQL compared to patients reporting no diarrhea . The range of difference between patients who reported very much diarrhea and those with none was 8-18 points for PF across trials. For HRQL scores, the range was 13–17 points worse. This trend was also seen in the control arm and at other times. Conclusions: In this set of breast cancer trials with differences in diarrhea by arm, reporting “no meaningful difference in PF or HRQL between the arms” is insufficient and potentially misleading. A more informative interpretation is that an exploratory analysis of HRQL and PF did not show in the investigational arm; there was a greater proportion of patients reporting diarrhea on the treatment arm; and patients reporting more frequent diarrhea reported lower HRQL and PF compared to patients with no diarrhea, regardless of arm. [Table: see text]

scholarly journals Study protocol: DexaDays-2, hydrocortisone for treatment of dexamethasone-induced neurobehavioral side effects in pediatric leukemia patients: a double-blind placebo controlled randomized intervention study with cross-over design

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
A. M. van Hulst ◽  
E. J. Verwaaijen ◽  
M. F. Fiocco ◽  
S. M. F. Pluijm ◽  
M. A. Grootenhuis ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Side Effects ◽  
Lymphoblastic Leukemia ◽  
Controlled Trial ◽  
Life Questionnaire ◽  
Dexamethasone Treatment ◽  
Double Blind ◽  
Pediatric Leukemia ◽  
Double Blind Placebo

Abstract Background Dexamethasone, a highly effective drug in treating pediatric acute lymphoblastic leukemia (ALL), can induce serious neurobehavioral side effects. These side effects are experienced by patients and parents as detrimental with respect to health related quality of life (HRQoL). Based on previous studies, it has been suggested that neurobehavioral side effects are associated to cortisol depletion of the mineralocorticoid receptor in the brain. Our previously reported randomized controlled trial, the Dexadagen study (NTR3280), suggests that physiological hydrocortisone addition during dexamethasone treatment may overcome clinically relevant neurobehavioral problems in patients who experience these problems during dexamethasone treatment. With our current study, we aim to replicate these results in a targeted larger sample before further implementing this intervention into standard of care. Methods In a national center setting, pediatric ALL patients between 3 and 18 years are enrolled in an Identification study, which identifies patients with clinically relevant dexamethasone-induced neurobehavioral side effects using the Strengths and Difficulties Questionnaire (SDQ). Contributing factors, such as genetic susceptibility, dexamethasone pharmacokinetics as well as psychosocial and family factors are studied to determine their influence in the inter-patient variability for developing dexamethasone-induced neurobehavioral side effects. Patients with clinically relevant problems (i.e. a rise of ≥ 5 points on the SDQ Total Difficulties Score after 5 days of dexamethasone) are subsequently included in a randomized double-blind placebo-controlled trial with a cross-over design. They receive two courses placebo followed by two courses hydrocortisone during dexamethasone treatment, or vice versa, each time at least 16 days without study medication in between. The primary endpoint is change in SDQ score. The secondary endpoints are sleep (measured with actigraphy and the Sleep Disturbance Scale for Children) and HRQoL (Pediatric Quality of Life Questionnaire). Discussion The results of our current study may contribute to the management of future ALL patients who experience dexamethasone-induced neuropsychological problems as it may improve HRQoL for patients who suffer most from dexamethasone-induced neurobehavioral side effects. Furthermore, by investigating multiple risk factors that could be related to inter-patient variability in developing these side effects, we might be able to identify and treat patients who are at risk earlier during treatment. Trial registration Medical Ethical Committee approval number: NL62388.078.17. Affiliation: Erasmus Medical Centre. Netherlands Trial Register: NL6507 (NTR6695). Registered 5 September 2017

scholarly journals The Pharmacopsychometric Triangle to Illustrate the Effectiveness of T-PEMF Concomitant with Antidepressants in Treatment Resistant Patients: A Double-Blind, Randomised, Sham-Controlled Trial Revisited with Focus on the Patient-Reported Outcomes

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
P. Bech ◽  
M. Gefke ◽  
M. Lunde ◽  
L. Lauritzen ◽  
K. Martiny
Keyword(s):  
Effect Size ◽  
Patient Reported Outcomes ◽  
Controlled Trial ◽  
Clinical Effects ◽  
Treatment Resistant ◽  
Double Blind ◽  
Patient Reported ◽  
Clinically Significant ◽  
Antidepressive Medication

Background. Our T-PEMF trial has been revisited with focus on the pharmacopsychometric triangle in which effect size is used when comparing wanted versus unwanted clinical effects and quality of life as outcomes. In this analysis, we have especially focused on the self-reported HAM-D6.Methods. The antidepressive medication which the patients were resistant to was kept unchanged during the five weeks of active versus sham T-PEMF.Results. In total 21, patients received active T-PEMF, and 19 patients received sham T-PEMF. The effect size was 1.02 and 0.90, respectively, on HAM-D6and HAM-D6-S. Concerning side effects, the active T-PEMF reduced the baseline score on concentration problems with an effect size of 0.44 while inducing more autonomic symptoms than sham T-PEMF with an effect size of −0.41. The advantage of active over sham T-PEMF obtained an effect size of 0.48.Conclusion. Active T-PEMF was found superior to sham T-PEMF within the pharmacopsychometric triangle with a clinically significant effect size level above 0.40.

Patient- versus physician-reported toxicities among survivors of head and neck cancer after chemoradiation: Prospective evaluation of screening methodologies.

2016 ◽  
Vol 34 (3_suppl) ◽  
pp. 150-150
Author(s):  
Allen M. Chen ◽  
Carol Felix ◽  
Sophia Hsu
Keyword(s):  
Quality Of Life ◽  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Voice Quality ◽  
Life Questionnaire ◽  
Exact Test ◽  
True Incidence ◽  
Patient Reported

150 Background: This study sought to compare the incidence of late toxicities among survivors of head and neck cancer treated by definitive chemoradiation using patient-reported versus physician-reported methodologies. Methods: Two validated quality of life instruments, the University of Washington Quality of Life questionnaire (UW-QOL) and the Functional Assessment of Cancer Therapy for Head and Neck questionnaire (FACT-H&N) were administered to patients returning for follow-up after chemoradiation for head and neck cancer. Only patients who had been clinically without evidence of disease for greater than 6 months were sampled. Scores were compared to physician-reported toxicities, which were recorded blindly and independently after each patient visit, using the National Cancer Institute’s Common Toxicity Criteria (version 4.0). Two by two contingency tables were constructed to assess differences between patient- and physician-reported responses using Fisher’s exact test. Results: Fifty patients (35 male; 15 females) completed both instruments. While 78% of patients reported an inability “to swallow certain solid foods” and 70% reported difficulty to “swallow naturally and easily” using the self-reported UW-QOL and FACT-H&N surveys, respectively, the incidence of grade 2+ esophageal dysfunction as reported by physicians was only 48% (p < 0.001). While 60% of patients reported “too little saliva” and 50% acknowledged having problems with "voice quality and strength" using the UW-QOL and FACT-H&N surveys, only 20% and 30%, respectively, were scored as having grade 2+ xerostomia and laryngeal toxicity. Significant discordance was also observed between patient- and physician-reported toxicities with respect to the domains of appearance (p = 0.02), pain (p = 0.01), activity/energy (p < 0.001), and mood (p = 0.001). Conclusions: Late toxicities are frequently under-reported by physicians after chemoradiation for head and neck cancer. The true incidence and severity of these treatment-related toxicities, with respect to both functional and psychosocial impairment, among survivors may be better evaluated by patient-reported methods.

scholarly journals Effects of a Few Minutes of Abdominal Drawing-in Maneuver on Balance Test Results

2021 ◽  
Keyword(s):  
Quality Of Life ◽  
Repeated Measures ◽  
Controlled Trial ◽  
Intervention Group ◽  
Educational Interventions ◽  
Control Group ◽  
Life Questionnaire ◽  
Menopausal Women ◽  
Significant Difference

Background: Menopause is a natural part of women's lives and is associated with a series of complications that can impair their quality of life. This study was conducted to determine the effect of educational interventions based on the Multi-Theory Model (MTM) on the quality of life among menopausal women. Methods: This randomized controlled trial was conducted on 80 menopausal women who met the inclusion criteria and were selected through the multi-stage stratified random sampling method. The participants were randomly allocated to either the control or intervention group (40 subjects per group). The intervention group participated in five 45-min educational sessions based on the MTM on the predetermined days of the week. The quality of life level scores were collected at baseline, immediately, and three months after the intervention using the Menopause-Specific Quality of Life questionnaire (MENQOL). On the other hand, the control group did not receive any intervention during the study period. Results: Analysis of variance of repeated measures showed a significant interaction between time and intervention. Therefore, the independent t-test was used to compare the mean score of quality of life, before, immediately, and three months after the intervention. The results showed a significant difference between the two groups regarding the scores immediately after and three months after the intervention. Conclusion: Structured educational program based on the MTM could be used as a simple and noninvasive intervention that helps menopausal women’s general health through menopausal symptoms relief, thereby improving their quality of life. Further interventions with larger sample sizes may be required to confirm these findings.

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