A randomized, double-blind, placebo-controlled, multicenter study assessing the efficacy of magnesium oxide monohydrate in the treatment of nocturnal leg cramps

Abstract Background Magnesium supplements are widely used for prophylaxis and treatment of nocturnal leg cramps (NLC). However, there is little evidence in support of their effectiveness. The main impediment stems from the lack of assessments of cellular absorption. In the current study, we tested the efficacy and safety of a magnesium supplement – magnesium oxide monohydrate (MOMH), for which increased cellular absorption rates were demonstrated in an ex-vivo setting. Methods A randomized, double-blind, placebo-controlled multicenter study was conducted in hospitals and outpatient clinics in Ukraine, from February to August 2018. Eligible subjects received a capsule with MOMH 226 mg or placebo, once daily, at bedtime, for a 60-day period. The assessed parameters included frequency and duration of NLC episodes, quality of sleep, NLC-induced pain and quality of life sub-scores. The Fisher’s Exact Test for comparison of groups by categorical variables was used. The Student’s test or Mann-Whitney test were used for between-group comparison at different timepoints. ANCOVA followed by contrast analysis was used for comparison of groups at the end of the study. Results 175 (81%) out of 216 initially screened subjects completed the study. The number of NLC episodes has significantly decreased by the end of the study period as compared to baseline in both groups (p < 0.001 for both). There was a significant between-group difference in the magnitude of reduction in NLC episodes (p = 0.01), indicating a higher decrease in the MOMH group as compared to the placebo group (− 3.4 vs − 2.6, respectively). In addition, MOMH treatment resulted in a greater reduction in NLC duration (p < 0.007) and greater improvement in sleep quality (p < 0.001) as compared to placebo. Conclusions MOMH was shown to be effective in the treatment of NLC as well as safe and well-tolerated. Trial registration NCT03807219, retrospectively registered on January 16, 2019.

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A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study Assessing the Efficacy of Magnesium Oxide Monohydrate in the Treatment of Nocturnal Leg Cramps

10.21203/rs.3.rs-395668/v2 ◽

2021 ◽

Author(s):

Olha Barna ◽

Pavlo Lohoida ◽

Yurii Holovchenko ◽

Andrii Bazylevych ◽

Valentyna Velychko ◽

...

Keyword(s):

Magnesium Oxide ◽

Multicenter Study ◽

Ex Vivo ◽

Categorical Variables ◽

Double Blind ◽

Once Daily ◽

Exact Test ◽

Double Blind Placebo ◽

Contrast Analysis

Abstract Background: Magnesium supplements are widely used for prophylaxis and treatment of nocturnal leg cramps (NLC). However, there is little evidence in support of their effectiveness. The main impediment stems from the lack of assessments of cellular absorption. In the current study, we tested the efficacy and safety of a magnesium supplement – magnesium oxide monohydrate (MOMH), for which increased cellular absorption rates were demonstrated in an ex-vivo setting. Methods: A randomized, double-blind, placebo-controlled multicenter study was conducted in hospitals and outpatient clinics in Ukraine, from February to August 2018. Eligible subjects received a capsule with MOMH 226mg or placebo, once daily, at bedtime, for a 60‑day period. The assessed parameters included frequency and duration of NLC episodes, quality of sleep, NLC-induced pain and quality of life sub-scores. The Fisher's Exact Test for comparison of groups by categorical variables was used. The Student’s test or Mann-Whitney test were used for between-group comparison at different timepoints. ANCOVA followed by contrast analysis was used for comparison of groups at the end of the study. Results: 175 (81%) out of 216 initially screened subjects completed the study. The number of NLC episodes has significantly decreased by the end of the study period as compared to baseline in both groups (p<0.001 for both). There was a significant between-group difference in the magnitude of reduction in NLC episodes (p=0.01), indicating a higher decrease in the MOMH group as compared to the placebo group (-3.4 vs -2.6, respectively). In addition, MOMH treatment resulted in a greater reduction in NLC duration (p<0.007) and greater improvement in sleep quality (p<0.001) as compared to placebo.Conclusions: MOMH was shown to be effective in the treatment of NLC as well as safe and well-tolerated. ClinicalTrials.gov identification number: NCT03807219, retrospectively registered on January 16, 2019.

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A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study Assessing the Efficacy of Magnesium Oxide Monohydrate in the Treatment of Nocturnal Leg Cramps

10.21203/rs.3.rs-395668/v1 ◽

2021 ◽

Author(s):

Olha Barna ◽

Pavlo Lohoida ◽

Yurii Holovchenko ◽

Andrii Bazylevych ◽

Valentyna Velychko ◽

...

Keyword(s):

Magnesium Oxide ◽

Multicenter Study ◽

Ex Vivo ◽

Categorical Variables ◽

Double Blind ◽

Exact Test ◽

Double Blind Placebo ◽

Study Results ◽

Contrast Analysis

Abstract Background Magnesium supplements are widely used for prophylaxis and treatment of nocturnal leg cramps (NLC). However, there is little evidence in support of their effectiveness. The main impediment stems from the lack of assessments of cellular absorption. In the current study, we tested the efficacy and safety of a magnesium supplement – magnesium oxide monohydrate (MOMH), for which increased cellular absorption rates were demonstrated in an ex-vivo setting. Methods A randomized, double-blind, placebo-controlled multicenter study was conducted in hospitals and outpatient clinics in Ukraine, from February to August 2018. Eligible subjects received a capsule with MOMH 226mg or placebo, once daily, at bedtime, for a 60day period. The assessed parameters included frequency and duration of NLC episodes, quality of sleep, NLC-induced pain and quality of life sub-scores. The Fisher's Exact Test for comparison of groups by categorical variables was used. The Student’s test or Mann-Whitney test were used for between-group comparison at different timepoints. ANCOVA followed by contrast analysis was used for comparison of groups at the end of the study. Results 175 (81%) out of 216 initially screened subjects completed the study. The number of NLC episodes has significantly decreased by the end of the study period as compared to baseline in both groups (p < 0.001 for both). There was a significant between-group difference in the magnitude of reduction in NLC episodes (p = 0.01), indicating a higher decrease in the MOMH group as compared to the placebo group (-3.4 vs -2.6, respectively). In addition, MOMH treatment resulted in a greater reduction in NLC duration (p < 0.007) and greater improvement in sleep quality (p < 0.001) as compared to placebo. Conclusions MOMH was shown to be effective in the treatment of NLC as well as safe and well-tolerated. ClinicalTrials.gov identification number: NCT03807219, retrospectively registered on January 16, 2019.

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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)

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.2071 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Cited By ~ 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.

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Phase 3, randomized, double-blind, placebo-controlled study of venetoclax combined with azacitidine versus azacitidine in treatment-naïve patients with acute myeloid leukemia.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.tps7069 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. TPS7069-TPS7069 ◽

Cited By ~ 2

Author(s):

Jalaja Potluri ◽

Tu Xu ◽

Wan-Jen Hong ◽

Mack H. Mabry

Keyword(s):

Overall Survival ◽

Myeloid Leukemia ◽

Remission Rate ◽

Controlled Study ◽

Phase 3 ◽

Double Blind ◽

Once Daily ◽

Double Blind Placebo ◽

Treatment Naïve

TPS7069 Background: Elderly acute myeloid leukemia (AML) is a biologically and clinically distinct disease with a diminished response to chemotherapy, low remission rates, and short disease-free and overall survival. Venetoclax (VEN) is a potent, selective small-molecular inhibitor of BCL-2. In preclinical models, venetoclax has been shown to kill AML cells as a single agent with demonstrated synergistic activity in combination with the DNA methyltransferase inhibitor azacitidine (AZA). Early clinical data from a phase 1b study (NCT02203773) showed that VEN plus AZA had an acceptable safety profile and promising efficacy in treatment-naïve elderly patients with AML. The current phase 3 study continues to evaluate the combination for this AML population. Methods: This phase 3, randomized, double-blind, placebo-controlled study (NCT02993523) is designed to assess VEN plus AZA compared with placebo plus AZA in treatment-naïve elderly and adult patients with AML who are not eligible for standard induction therapy due to age or comorbidities. Primary objectives of the study are to evaluate if VEN with AZA will improve overall survival (OS) and composite complete remission rate (CR+CRi) versus placebo with AZA. Secondary objectives include event-free survival, CR+CRi rate at the end of Cycle 1, and if combining VEN plus AZA reduces fatigue and improves global health status/quality of life based on patient reported outcomes versus placebo with AZA. Exploratory objectives are to evaluate biomarkers predictive of VEN activity including minimal residual disease negativity rate, and BCL-2 expression and outcome measures of overall survival and complete remission rate, as well as the impact of VEN on additional quality of life measures. Patients will be randomized 2:1 to VEN plus AZA (arm A) or placebo plus AZA (arm B). Patients on arm A will receive once daily 400 mg VEN orally on days 1–28 plus daily 75 mg/m2 SC or IV AZA for 7 days in a 28-day cycle. Patients on arm B will receive once daily placebo orally on days 1–28 plus daily 75 mg/m2 SC or IV AZA for 7 days on a 28-day cycle. Study recruitment began in February 2017, with target enrollment of 400 patients. Clinical trial information: NCT02993523.

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