Clinical trial NCT03526523: Testing the Efficacy of Mindfulness-based Stress Reduction in the Prevention of Perimenopausal Depression
Official title: Testing the Efficacy of Mindfulness-based Stress Reduction as a Prophylactic Intervention in the Prevention of Perimenopausal Depression: a Randomized Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Perimenopausal Depression
Depressive Symptoms
Keywords: Mindfulness based stress reduction
Perimenopausal depression
Menopause transition
Lead sponsor: University of Regina
Sponsor class: OTHER
Collaborators: name: Saskatchewan Health Research Foundation
name: Saskatchewan Centre for Patient-Oriented Research
name: University of Calgary
name: Saskatchewan Health Authority - Regina Area
First posted: 2018-05-16
Enrollment: 104
Sex: FEMALE
Minimum age (years): 42
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A stratified randomization method will be used to balance the number of baseline stressful life events in each treatment group (\<3 vs. 3+ in the last 6 months). Randomization will be performed once baseline stressful life events are determined.
Primary purpose: PREVENTION

Brief summary: Depression is the leading cause of disability worldwide and a risk factor for other diseases. While women are at elevated risk for depression in general, the menopause transition is a particularly vulnerable time for many women, with the risk for depression increasing 2-4 fold. The objective of this research study is to determine whether mindfulness-based stress reduction (MBSR), an 8-week structured intervention involving meditation and yoga, has any beneficial mood effects for women undergoing this vulnerable time.

Detailed description: The menopause transition (a.k.a. perimenopause) represents the reproductive stage transitioning from regular menstrual cycles through the loss of ovulatory function and to the complete cessation of menses. The latter marks the onset of menopause. All middle-aged women experience the menopause transition, which, on average, extends 5-6 years surrounding the last menstrual period. In Saskatchewan, roughly 80 000 women are currently of perimenopausal age. An estimated 26-33% of women develop clinically significant depressive symptoms during the perimenopause. Rates of diagnosed major depressive disorder during the menopause transition range between 12 and 23%. Mounting evidence findings from the PI and others suggests that the erratic fluctuations in estradiol that occur during the normal menopause transition play a key role. Specifically, increased estradiol fluctuation may increase one's sensitivity to stress both in the laboratory and in the context of real-world stressful life events, resulting in an increased risk for clinically significant depressive symptoms.

MBSR has proven to be very effective at increasing stress resilience and improving emotional wellbeing in a variety of populations. Thus, in the current SHRF-funded project, we will examine the prophylactic mood benefits of MBSR. We hypothesize that MBSR will increase women's resilience in the context of stress-sensitizing hormonal fluctuation in the menopause transition, making them less prone to developing depressive symptoms.

The current project will be composed of five components: 1) Enrollment session; 2) Hormonal Sensitivity Assessment (1 month); 3) Treatment Phase (8 weeks); 4) Follow-Up Phase (6 months) and 5) Waitlist Control Group Treatment (8 weeks). Each component is described in detail below:

1. Enrollment Session. After completing an eligibility screening over the phone, a trained research assistant (RA) will conduct an enrollment session over the phone with the prospective participant. The participant will be emailed a Powerpoint presentation summarizing the study and a link to a Qualtrics survey that will contain an electronic version of the consent form. Over the phone, the RA will review the Powerpoint slides and consent form. Once consent is obtained, the RA will administer the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders-5 (SCID-RV) for axis I disorders to screen for the presence of current psychiatric disorders as well as assess past major depressive episodes. The participant will then follow the RA's instructions on how to download the Expimetrics application on their smart phone, which they will use to complete study component #2 (described below). After the phone call, participants will be emailed a link to a Qualtrics survey containing a number of questionnaires assessing demographic information as well as psychological variables that may predict participant outcomes. The RA will instruct the participant to complete the survey at their convenience over the following 7 days. The RA will also mail a kit containing 12 2-ml vials contained in a small cardboard box and 10 ovulation predictor tests. Next, participants will complete an electronic version of a number of questionnaires, described below, with the use of Qualtrics. Finally, participants will be given instructions on how to take an ovulation test and how to collect urine samples at home.
2. Hormonal Sensitivity Assessment (1.5 months). Starting on the first day of their next menstrual period following the enrolment session, participants will complete the Daily Rating of Severity of Problems (DRSP) for approximately 45 days (if possible, using the Expimetrics smart phone app). Starting on day seven of their menstrual cycle, they will take an ovulation predictor test upon waking each day until a positive test is obtained (usually 6-8 days). Once a positive test is obtained, the participant will notify a research assistant by text, email or phone. In addition, they will be asked to collect a small sample of urine every other day for 30 days. The DRSP should be completed daily until the last day of urine collection.
3. MBSR Intervention (8 weeks). The intervention is provided over the course of eight weekly 150-minute sessions and one 7-hour weekend intensive silent retreat. The MBSR program, modeled after the work of Jon Kabat-Zinn and colleagues at the Stress Reduction and Relaxation Clinic-Massachusetts Medical Center, has been used and adapted by Dr. Campbell and his colleagues at the University of Calgary for numerous populations. The MBSR program consists of three primary components: 1) theoretical material related to relaxation, meditation, and the body-mind connection, 2) experiential practice of meditation and yoga during the group meetings and home based practice, and 3) group process focused on problem solving related to impediments to effective practice, practical day-to-day applications of mindfulness, and supportive interaction between group members. A booklet is distributed containing information pertinent to each week's instruction, including a bibliography for those wishing to pursue relevant themes in greater depth, and 2 CDs with guided meditation to help with home practice. Each week, participants will be asked to record all between-session home practice.

   All sessions will be audiotaped; audiotapes will be randomly selected to be viewed by Dr. Campbell to monitor treatment fidelity. After evaluating the tapes, both written and verbal feedback will be provided to the instructor to support compliance with the treatment protocol. Note that audiotapes will not reveal the identity of any of the participants.
4. Follow-up Period (6 months). Immediately following the intervention and every two weeks for 6 months, participants from both treatment groups will be emailed a link to a Qualtrics survey including the CES-D. The following questionnaires will also be included in the survey immediately following the intervention as well as months 2, 4 and 6: the Perceived Stress Scale, the State-Trait Anxiety Inventory, the Five Facet Mindfulness Questionnaire and the Connor-Davidson Resilience Scale. For participants without an email address, an RA will complete the survey with them over the phone. Participants obtaining a CES-D score ≥16 will be contacted by an RA to complete the mood module of the SCID-5 over the phone to identify cases of major depression. Importantly, all post-randomization correspondence with participants will be carried out by staff members who are blinded to participants' treatment condition.
5. Waitlist MBSR Intervention (8 weeks). Following the six-month follow-up, members of each wave's waitlist control group will receive the MBSR intervention. Although this will serve no research purpose, we believe offering MBSR to all participants, rather than using a "no treatment" condition will make the trial more equitable and appealing.

Eligibility criteria: Inclusion Criteria:

* in the early or late menopause transition according to the Stages of Reproductive Aging Workshop (STRAW+10) criteria, defined as menstrual cycle length 7+ days shorter or longer than usual or the presence of amenorrhea lasting 60 days or more (but less than 12 months)

Exclusion Criteria:

* current psychiatric diagnosis of major depressive disorder, bipolar disorder, a psychotic disorder or any other psychiatric diagnosis rated "severe" based on DSM-5 criteria
* use of medications affecting mood (e.g. antidepressants) or ovarian hormone levels (e.g. oral contraceptives)
* pregnant or nursing
* currently receiving a psychological treatment for depression
* major life-threatening health conditions.

Primary outcomes:
measure: Depressive symptoms
timeFrame: 6 months (CES-D completed every 2 weeks)
Secondary outcomes:
measure: Occurrence of elevated depressive symptoms (ordinal)
timeFrame: 6 months (CES-D completed every 2 weeks)
measure: Occurrence of elevated depressive symptoms (binary)
timeFrame: 6 months (CES-D completed every 2 weeks)
measure: Occurrence of major depressive episodes
timeFrame: 6 months (SCID is administered in instances where a score of 16 or above is obtained on the Center for Epidemiologic Studies Depression Scale)
Other outcomes:
measure: Perceived stress
timeFrame: 6 months (PSS is completed at months 0, 2, 4 and 6)
measure: Stress resilience
timeFrame: 6 months (completed at months 0, 2, 4 and 6)
measure: Trait Anxiety
timeFrame: 6 months (completed at months 0, 2, 4 and 6)
Locations:
city: Regina
country: Canada
facility: University of Regina, Department of Psychology
state: Saskatchewan
Study officials:
affiliation: University of Regina
name: Jennifer L Gordon, PhD
role: PRINCIPAL_INVESTIGATOR
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