Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT06306404 |
| Other study ID # |
NL86165.100.24 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
June 1, 2024 |
| Est. completion date |
June 1, 2028 |
Study information
| Verified date |
March 2024 |
| Source |
VU University of Amsterdam |
| Contact |
Anne-Sophie Koning, Dr. |
| Phone |
+31 20 566 5500 |
| Email |
a.koning[@]nin.knaw.nl |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The perimenopause is known as a vulnerable period for some women, with noticeable somatic and
psychological issues. Aside from climacteric symptoms, insomnia and depression are common.
About half of women during the peri-menopausal period experience sleep problems like problems
falling asleep, awakening during the night and being unable to return to sleep. This is often
attributed to vasomotor symptoms, but this is not the only reason of poor sleep (Joffe et
al., 2010). Also, the peri-menopausal period is a critical time for the occurrence of new
onset and recurrent depressions (Cohen et al., 2006). It has been suggested that fluctuations
in estradiol may increase the risk for depression by altering neuronal functions in the
brain. But there are also indications that the risk for depression increases by indirect
effects, such as the increase in insomnia. Poor sleep has increasingly been recognized as the
key modifiable factor affecting mental issues like depression (Van Someren, 2021). While
antidepressants and psychotherapies continue to be the treatments of choice for depression,
and Cognitive Behavioral Therapy for sleep (CBTi) for insomnia, preclinical and clinical data
support the benefits of estrogen-based therapies to improve mood, sleep and other
menopause-related symptoms (Gordon et al. 2018). Transdermal estradiol patches, which provide
a stable release of estradiol and lead to more stable blood levels, have been suggested to
have a positive effect on sleep (Joffe et al., 2020) and depressive symptoms (Gordon et al.,
2018) in randomized controlled trials. However, it is currently unclear if the relation
between improvement in mood and estradiol patches is mediated by improvement in sleep
problems, and if the effect of estradiol patches on sleep problems is more effective during
peri-menopause than the current evidence-based sleep interventions of CBTi, preferably in
combination with Circadian Rhythm Support (CRS). The aim of the study is to pinpoint the
determinants of complaints about sleep and mood and how they respond to Menopausal Hormone
Treatment (MHT) with and without the addition of a guided eHealth sleep intervention that
combines CBTi + CRS.
Measurements will be conducted at baseline (T0), 2 months (T1) and 4 months (T3), with
questionnaires, sleep measurements (EEG sleepband and actigraph) and skin conductance (to
measure hot flushes). Participants will be recruited via www.slaapregister.nl and via OLVG
outpatient clinic population of peri-menopausal women seeking help for climacteric complaints
(like hot flushes, feeling bloated, increase in weight), including sleep problems. The
participants are adults between 40-55 years old, with an Insomnia Severity Index score ≥10
and Climacteric Green Scale score ≥ 13.They have the self-considered capability to complete
online questionnaires and diaries in Dutch.
The intervention will be MHT (estradiol transdermal patches 50 mcg (Systen), in combination
with 200 mg progesterone (Utrogestan tablets for 2 weeks, adjusted to the menstrual cycle to
prevent endometrium carcinoma according to the international MHT guidelines), with and
without the addition of a guided eHealth sleep intervention that combines CBTi + CRS.
Description:
The primary outcome measure is insomnia severity (Bastien et al., 2001). Secondary outcomes
address five domains: depressive symptoms, symptoms of other mental health symptoms,
climacteric symptoms, daytime functioning and well-being and other sleep measurements. The
severity of mental health complaints characterizing different diagnostic dimensions, as well
as well-being and daytime functioning including health behaviours and use of care, all
assessed by online survey or clinical interview at T0, T1 (2 months) and T2 (4 months).
Climacteric symptoms are assessed with the Green Climacteric Scale at T0, T1, T2. Hot flashes
are measured with ambulatory sternal skin conductance monitoring (Purplexus). The other sleep
measures include other indicators of sleep and overnight alleviation of distress assessed
from the Carney Consensus Sleep Diary, kept online for a week; rest-activity rhythm and
activity-based sleep estimates obtained with an actigraph at 7 baseline nights (T0), 7
post-interventions nights (T1) and 7 follow-up nights (T2); objective sleep efficiency, REM
sleep fragmentation and heartrate with an ambulatory headband EEG at 5 baseline nights (T0),
5 post-interventions nights (T1) and 5 follow-up nights (T2).
