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Neurokinin 3 receptor antagonism as a novel treatment for menopausal hot flushes: a phase 2, randomised, double-blind, placebo-controlled trial
- Publication Year :
- 2017
- Publisher :
- Elsevier: Lancet, 2017.
-
Abstract
- Background Hot flushes affect 70% of menopausal women and often severely impact physical, psychosocial, sexual, and overall wellbeing. Hormone replacement therapy is effective but is not without risk. Neurokinin B signalling is increased in menopausal women, and has been implicated as an important mediator of hot flushes. Methods This phase 2, randomised, double-blind, placebo-controlled, single-centre, crossover trial assessed the effectiveness of an oral neurokinin 3 receptor antagonist (MLE4901) on menopausal hot flushes. Eligible participants were healthy women aged 40–62 years, having seven or more hot flushes in every 24 h of which some were reported as being severe or bothersome, who had not had a menstrual period for at least 12 months, and who had not been taking any medication shown to improve menopausal flushes in the preceding 8 weeks. Participants received 4 weeks of MLE4901 (40 mg, orally, twice daily) and placebo (orally, twice daily) in random order separated by a 2 week washout period. Randomisation was completed by a central computer, and participants were allocated to treatment number in numerical order. The primary outcome was the total number of hot flushes during the final week of both treatment periods. Analyses were by intention to treat and per protocol using generalised linear mixed models and standard crossover analysis. All analyses were prespecified in the study protocol. The trial is registered at ClinicalTrials.gov, number NCT02668185. Findings 68 women were screened between Feb 3 and Oct 10, 2016, of which 37 were randomly assigned and included in an intention-to-treat analysis. 28 participants completed the trial and were included in a per-protocol analysis. MLE4901 significantly reduced the total weekly number of hot flushes by 45 percentage points (95% CI 22–67) compared with the placebo (intention-to-treat adjusted means: placebo 49·01 [95% CI 40·81–58·56] vs MLE4901 19·35 [15·99–23·42]; adjusted estimate of difference 29·66 [17·39–42·87], p
- Subjects :
- Adult
Hormone Replacement Therapy
NIGHT SWEATS
VASOMOTOR SYMPTOMS
Medicine, General & Internal
Double-Blind Method
General & Internal Medicine
Humans
NUCLEUS
NEURONS
TEMPERATURE
11 Medical and Health Sciences
GENE-EXPRESSION
Science & Technology
Cross-Over Studies
FLASHES
WOMEN
Receptors, Neurokinin-3
Middle Aged
HYPERTROPHY
Treatment Outcome
Hot Flashes
Female
KISSPEPTIN
Menopause
Life Sciences & Biomedicine
Subjects
Details
- Database :
- OpenAIRE
- Accession number :
- edsair.od......1032..bcd54c4878f9bff87b50eb3f4cc85876