NCT06497894

Brief Summary

The goal of the clinical trial is to learn if Hormone Replacement Therapy (HRT) and Cognitive Behavioral Therapy (CBT-I) can treat insomnia in menopausal women. The main questions it aims to answer are:

  • Are HRT and CBT-I effective in reducing insomnia in menopausal women?
  • Are HRT and CBT-I comparable in terms of reducing insomnia severity in this population? Researchers will compare HRT and CBT-I to an active control group, receiving sleep hygiene instructions. Participants will:
  • Complete a screening and baseline assessment
  • Receive Hormone Replacement Therapy (as prescribed), Cognitive Behavioral Therapy (1/week), or sleep hygiene instructions (1/week) for 8 weeks.
  • Keep a daily diary (sleep e-diary), to assess sleep-quality.
  • Wear an electroencephalogram (EEG) during 6 nights (3 at baseline \& 3 post-intervention), to assess deep sleep cycles and waking episodes.
  • Receive a phone call for intervention compliance
  • Complete a post-intervention assessment.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
54

participants targeted

Target at P25-P50 for phase_4

Timeline
9mo left

Started Jan 2026

Shorter than P25 for phase_4

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress32%
Jan 2026Jan 2027

First Submitted

Initial submission to the registry

July 4, 2024

Completed
8 days until next milestone

First Posted

Study publicly available on registry

July 12, 2024

Completed
1.5 years until next milestone

Study Start

First participant enrolled

January 1, 2026

Completed
6 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2026

Expected
7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 30, 2027

Last Updated

January 13, 2026

Status Verified

January 1, 2026

Enrollment Period

6 months

First QC Date

July 4, 2024

Last Update Submit

January 12, 2026

Conditions

Keywords

PerimenopauseInsomniaCognitive Behavioral TherapyHormone Replacement Therapy

Outcome Measures

Primary Outcomes (1)

  • Reduction of Insomnia Severity

    Change from baseline in Insomnia Severity Index (ISI). The ISI is a seven-item questionnaire, asking respondents to rate the severity of sleep-related symptoms on 5-point Likert scales (Ranging between 0 = not applicable and 4 = very strong). Total values may range between 0 and 28, where 0 indicates no presence of sleep-related symptoms and 28 indicates very severe symptoms.

    Week 10

Secondary Outcomes (3)

  • Improvement in Climacteric Syndrome

    Week 10

  • Changes in bio-functional age

    Week 10

  • Changes in maladaptive sleep-related cognitions

    Week 10

Study Arms (3)

Cognitive Behavioral Therapy for insomnia (CBT-I)

EXPERIMENTAL

Participants in this experimental arm will receive cognitive behavioral therapy specifically designed to treat insomnia (CBT-I). The therapy will be delivered over 8 weekly sessions, each lasting 60 minutes. The sessions will include techniques such as sleep restriction, stimulus control, cognitive restructuring, and relaxation training. The primary goal is to improve sleep quality and reduce the severity of insomnia.

Behavioral: Cognitive Behavioural Therapy for Insomnia (CBT-I)

Hormone Replacement Therapy (HRT)

ACTIVE COMPARATOR

Participants in this experimental arm will receive hormone replacement therapy, specifically a combination of estrogen and progesterone over the course of 8 weeks. The therapy aims to alleviate menopausal symptoms, including insomnia, by addressing hormonal imbalances.

Drug: Hormone Replacement Therapy (HRT)

Sleep Hygiene

SHAM COMPARATOR

Participants in this sham comparator arm will receive sleep hygiene instructions. Instructions will be delivered over 8 weekly sessions. The instructions will provide general information about healthy sleep habits, such as food and drink choices, a regular sleep schedule, evening routine, etc. Although being widely used in daily clinical practice, sleep hygiene shows no significant effect as monotherapy in patients with an established insomnia. The sleep hygiene condition in this study is matched to CBT-I in frequency and intensity of contact.

Behavioral: Sleep Hygiene

Interventions

CBT-I is conducted in an individual setting according to the manual used in McCurry (1). Factors at the level of behavior, cognitions, and physiology that perpetuate sleep onset and sleep maintenance disorders are addressed. In addition, psychoeducation on sleep and sleep hygiene, stimulus control, sleep restriction, relaxation, structured worry time, cognitive restructuring, and relapse prevention are part of the training. Each session will include homework.

Cognitive Behavioral Therapy for insomnia (CBT-I)

Standard-dose continuously-combined bio-identical HRT containing transdermal estradiol 1.5 mg/d (= 2 strokes of Oestrogel® Dispenser) and oral micronized progesterone (= 1 capsule of Utrogestan® 200). This combination is the most popular HRT regimen, as it has a neutral effect on lipids, glucose, haemostasis. Participants will receive a conventional prescription for the 2 products that are covered by all health insurances in Switzerland.

Hormone Replacement Therapy (HRT)
Sleep HygieneBEHAVIORAL

Sleep hygiene refers to healthy sleep habits, e.g. food and drink choices, a regular sleep schedule, evening routine. Although being widely used in daily practice, sleep hygiene shows no significant effect as monotherapy in patients with an established insomnia. The sleep hygiene condition in this study is matched to CBT-I in frequency and intensity of contact.

Sleep Hygiene

Eligibility Criteria

Age45 Years - 69 Years
Sexfemale
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Late menopausal transition according to Stages of Reproductive Aging criteria (STRAW+10)
  • Pittsburgh Sleep Quality Index (PSQI) score \> 5
  • Insomnia Severity Index (ISI) score \> 7
  • Somato-vegetative domain of the Menopause Rating Scale (MRS)-II ≥ 4 points
  • Willingness to use HRT for menopausal symptom reliefs

You may not qualify if:

  • Other sleep-wake disorders according to DSM-5, assessed with validated questionnaires (Sleep-Health Questionnaire, Epworth Sleepiness Scale (ESS))
  • Untreated hormonal disorder
  • Obesity (BMI ≥ 30)
  • Current psychotherapy
  • Current psychopharmacological therapy including regular sleep medication
  • History of unsuccessful CBT-I
  • Psychiatric illness
  • Substance abuse (≥ 7 cigarettes/day, no more than 2 standard WHO drinks per day, other drugs)
  • Shift work
  • Long-haul flights across different time zones in the past 3 months
  • Pregnancy and lactation
  • Contraindications to HRT according to drug information (https://www.swissmedicinfo.ch/)
  • Inability to follow procedures or insufficient knowledge of project language
  • Inability to give consent

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University Hospital of Bern, Department of Gynecological Endocrinology & Reproductive Medicine

Bern, 3010, Switzerland

RECRUITING

Related Publications (1)

  • Pavicic E, Stute P, Rudzik F, Urech A, Lozza-Fiacco S. No more sleepless nights in perimenopause-an open-label, randomized, parallel-group, active controlled intervention study in perimenopausal women with vasomotor symptoms and insomnia to investigate the efficacy of hormone replacement therapy and cognitive behavioral therapy for the treatment of insomnia: study protocol. Trials. 2025 Dec 30;27(1):94. doi: 10.1186/s13063-025-09366-9.

MeSH Terms

Conditions

Sleep Initiation and Maintenance Disorders

Interventions

Cognitive Behavioral TherapyHormone Replacement Therapy

Condition Hierarchy (Ancestors)

Sleep Disorders, IntrinsicDyssomniasSleep Wake DisordersNervous System DiseasesMental Disorders

Intervention Hierarchy (Ancestors)

Behavior TherapyPsychotherapyBehavioral Disciplines and ActivitiesDrug TherapyTherapeutics

Study Officials

  • Petra Stute, Prof.

    University Hospital of Bern, Department of Gynecological Endocrinology & Reproductive Medicine

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Petra Stute, Prof.

CONTACT

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 4, 2024

First Posted

July 12, 2024

Study Start

January 1, 2026

Primary Completion (Estimated)

July 1, 2026

Study Completion (Estimated)

January 30, 2027

Last Updated

January 13, 2026

Record last verified: 2026-01

Data Sharing

IPD Sharing
Will not share

Locations