Clinical trial NCT03838523: Non-concealed Placebo Treatment for Menopausal Hot Flushes
Official title: Non-concealed Placebo Treatment for Menopausal Hot Flushes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hot Flashes
Lead sponsor: Universitätsklinikum Hamburg-Eppendorf
Sponsor class: OTHER
First posted: 2019-02-12
Enrollment: 100
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Women with ≥5 daily moderate to severe hot flushes of at least moderate bother are assigned 1:1 to a 4-week OLP treatment or no treatment. To explore the duration and maintenance of placebo effects, participants in the OLP group are randomized a second time and divided into two subgroups who either discontinue (OLP 4wk) or continue the OLP treatment (OLP 8wk) for another 4 weeks.
Primary purpose: TREATMENT

Brief summary: It has been long viewed that placebos cannot be administered in accordance with ethical values because deception is instrumental to the placebo effect. This notion has been shaken up by studies on open-label placebos, showing that placebos can lead to positive effects even though their inert nature is disclosed.

Beneficial effects of double-blind placebos were found to be high in hot flush trials.

The objective of the study is to determine whether an open-label placebo (OLP) treatment is efficacious in alleviating hot flushes and bother among peri- and postmenopausal women.

Detailed description: Beneficial effects of double-blind placebos were found to be high in hot flush trials. Recent studies demonstrating the efficacy of placebos without concealment provide a possible way to administer placebos in accordance with ethical and clinical values.

The objective of the study is to determine whether an open-label placebo (OLP) treatment is efficacious in alleviating hot flushes and bother among peri- and postmenopausal women.

In this assessor-blinded, randomized-controlled trial, women with ≥5 daily moderate to severe hot flushes of at least moderate bother are assigned 1:1 to a 4-week OLP treatment or no treatment. Both groups are informed about study objectives including a briefing about the inert nature of placebo pills, why OLP might be effective and the importance of the control group. To explore the duration and maintenance of placebo effects, participants in the OLP group are randomized a second time and divided into two subgroups who either discontinue (OLP 4wk) or continue the OLP treatment (OLP 8wk) for another 4 weeks. All participants receive three study visits: at enrolment, baseline (1 week later), and at post-treatment. A fourth study visit is conducted at 8-week follow-up with the two subgroups OLP 4wk and OLP 8wk. Qualitative interviews about subjective experiences with the OLP treatment are conducted with n = 8 women.

This trial will contribute to the evaluation of OLP treatments in clinical practice and further our understanding about the magnitude of placebo effects in hot flush treatments.

Eligibility criteria: Inclusion Criteria:

* at least 5 moderate or severe hot flushes per day, including night time
* all hot flushes have at least moderate ratings of bother (sum score ≥ 16 on the bother subscale of the Hot Flush Rating Scale (HFRS) \[41\]
* fluency in German language
* participants are in menopausal transition (irregularities ≥ 60 days in the past year), or postmenopausal (cessation of menstruation ≥ 1 year) \[42\].

Exclusion Criteria:

* use of hormonal therapy to treat hot flushes within the last 6 weeks before enrolment
* use of herbal remedies to treat hot flushes within the last 6 weeks before enrolment
* intake of selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRI) within the last 6 weeks before enrolment
* previous oophorectomy
* severe physical or cognitive impairments which would constitute a barrier to give informed consent
* severe depression and anxiety (≥ 9 sum score or ≥ 5 depression or anxiety subscore on the Patient Health Questionnaire-4)
* medical conditions which might interact with menopausal hot flushes such as untreated hyperthyroidism, alcohol abuse (excluded when ≥4 on AUDIT-C) and cancer

Primary outcomes:
measure: Difference in hot flush composite score
timeFrame: 4 weeks
measure: Bother by hot flushes
timeFrame: 4 weeks
Secondary outcomes:
measure: Hot flush frequency
timeFrame: 4 weeks
measure: Health-related quality of life
timeFrame: 4 weeks
measure: Global improvement
timeFrame: 4 weeks
measure: Number of responders at week 4
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Hamburg
country: Germany
facility: University Medical Center Hamburg-Eppendorf
Study officials:
affiliation: Universitätsklinikum Hamburg-Eppendorf
name: Yvonne Nestoriuc, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Guttuso T Jr, Kurlan R, McDermott MP, Kieburtz K. Gabapentin's effects on hot flashes in postmenopausal women: a randomized controlled trial. Obstet Gynecol. 2003 Feb;101(2):337-45. doi: 10.1016/s0029-7844(02)02712-6.
citation: Hunter, M. S. The women's health questionnaire: A measure of mid-aged women's perceptions of their emotional and physical health. Psychology & Health, 7(1), 45-54, 1992.
citation: Shin H, Shin HS. Measurement of quality of life in menopausal women: a systematic review. West J Nurs Res. 2012 Jun;34(4):475-503. doi: 10.1177/0193945911402848. Epub 2011 Mar 25.
citation: Pan Y, Meister R, Lowe B, Winkelmann A, Kaptchuk TJ, Buhling KJ, Nestoriuc Y. Non-concealed placebo treatment for menopausal hot flushes: Study protocol of a randomized-controlled trial. Trials. 2019 Aug 16;20(1):508. doi: 10.1186/s13063-019-3575-1.