Clinical trial NCT03564041: SSM vs HEP in Late-Life Depression
Official title: Alternative Treatments to Help Late-Life Depression Study Protocol
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Late-life Depression
Treatment-resistant Depression
Keywords: depression
late-life
executive functioning
sahaj samadhi
meditation
treatment-resistant
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
First posted: 2018-06-20
Enrollment: 95
Sex: ALL
Minimum age (years): 60
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study will be a blinded (rater, investigator, and clinician), 12-week randomized controlled trial (RCT) conducted at Western University, London, ON, Canada, and McGill University, Montreal, QC, Canada.
Primary purpose: TREATMENT

Brief summary: The investigators will conduct a randomized controlled trial (RCT), comparing SSM (n=96) versus HEP (n=96) in 192 LLD participants stratified by site and presence of treatment resistant late life depression (TR-LLD). Participants will be blinded to the treatment hypothesis while investigators, raters and treating clinicians will be additionally blinded to the intervention. Both SSM and HEP will be taught over 4 consecutive days in similar sized groups (4-10 participants) followed by weekly reinforcement sessions for subsequent 11 weeks. Trained raters will collect data on depression symptoms (HAM-D 17 scale) and cognition at baseline, 12-week and 26-week follow-up as the primary and secondary outcome measures respectively.

Detailed description: RECRUITMENT AND CONSENT:

Participants will either be recruited from primary-, secondary-, and tertiary-care centres or from self-referral (general public). Montreal patients will be recruited from the Douglas Institute and associated Integrated University Health and Social Services Centres (CIUSSS)-Ouest de l'ile Local Community Services Centres (CLSCs) (CLSC Verdun and CLSC Lasalle), Jewish General Hospital (JGH) Psychiatry clinics (Institute for Community and Family Psychiatry) and associated CIUSSS-Centre-Ouest family medicine clinics/CLSCs: CLSC Benny Farm, CLSC Rene Cassin, CLSC Côte Des Neiges, CLSC Metro, CLSC Parc Extension, Herzl Family Medicine JGH, St-Mary's Dept. of Psychiatry, and McGill University Health Centre (MUHC) Dept. of Psychiatry. London participants will be recruited from London Health Science Centre (LHSC) sites (Victoria Hospital and University Hospital) and Parkwood Institute - Mental Health Care Building. Participants will be screened for eligibility and given a letter of information (LOI) for their review. After 24 hours, a research assistant will contact the participant and, if they are interested in participating and eligible to participate in the research study, they will be recruited into the study after valid consent is received.

STUDY INTERVENTION:

This study is a 12-week, randomized controlled trial seeking to recruit 192 participants with late-life depression total across two sites - (1) McGill University, Montreal, Quebec (QC), and (2) University of Western Ontario in London, Ontario (ON). Participants will be randomly assigned to one of two conditions: Sahaj Samadhi Meditation (SSM) or the Health Enhancement Program (HEP). The SSM intervention will be offered by trained and certified teachers from the Art of Living Foundation at Montreal and London between August 2018 and August 2021. The HEP intervention will be offered by a trained Nurse Practitioner, Social Worker, Psychologist, Occupational Therapist or other qualified professional at Montreal and London between August 2018 and August 2022. Raters, clinicians, and care providers will be blind to participant study condition.

SSM (the experimental group) and HEP (the active control group) require participants to attend training for 4 days, attend weekly follow-up sessions, and to practice the trained techniques at home for 20-minutes per day (details of each intervention can be found below). Participants will additionally be asked to fill out "homework logs" to record days they practiced the trained technique. A total of 3 assessment sessions are planned for participants to attend: to occur at baseline (0-week) as well as at 12-week and 26-week follow-ups.

MENTAL HEALTH ASSESSMENTS:

Participants will be screened using the Screening for Cognitive Impairment in Older Adults (Mini-Cog), Patient Health Questionnaire (PHQ-9), the Magnetic Resonance Imaging (MRI) pre-screening questionnaire, the Mini International Neuropsychiatric Interview, the Test of Premorbid Functioning, and the Antidepressant Treatment History Form (ATHF). Participants will be tested for the primary outcome, depression, using the Hamilton Depression Rating Scale (HAM-D17). The secondary outcome, executive functioning, will be measured by the Wechsler Adult Intelligence Scale (WAIS) Digit Span, Delis-Kaplan (D-KEFS) Verbal Fluency Test, Rey-Osterrieth Complex Figure-Copy Trial, and the California Verbal Learning Test-II-Short Form. Measures of primary and secondary outcomes will be administered at all 3 assessment sessions. All measures are described below.

BLOOD DRAW:

Blood draws will be performed at baseline (0-weeks) and 12-week follow-up by a qualified nurse at the CLSC in Montreal and Parkwood Mental Health in London. The blood collected will be stored at the Douglas Mental Health University Institute in Montreal, QC, and at Robart's Research Institute in London, ON.

GAIT:

Gait data will be collected in London, Ontario, only. The data to be collected is weight, height, waist circumference, and hip circumference. Gait data will be measured alongside the Falls Efficacy Scale (FES-I) (described below).

MRI:

The investigators aim to recruit a total of 50 participants (25 from each group) from the SSM/HEP study into a magnetic resonance imaging (MRI) study that will involve MRI scans at baseline and at the 12-week follow-up. Participants eligible for this sub-study will have had to complete the MRI pre-screening questionnaire. Those who are part of this sub-study will be invited to attend two MRI scanning sessions, which are expected to take about 1.5 h, to occur at baseline and the 12-week follow-up. Each MRI appointment will be completed in addition to the tasks described above.

STATISTICAL ANALYSIS

Descriptive statistics will be run with continuous variables summarized using mean and standard deviations and categorical variables summarized using counts and proportions. HDRS-17 scores at baseline and 12-week follow-up of patients assigned to SSM and HEP will be compared using linear mixed models. This approach will account for the clustering of observations, since both SSM and HEP will be delivered in a group setting. Next, we will evaluate whether a greater proportion of patients assigned to SSM, compared to HEP, achieve depression remission (defined as a HDRS-17 score ≤7 at the 12-week follow-up) using generalized linear mixed models.

We will take Z-scores of executive functioning tests at baseline and at 12-week follow-up for each test and take the mean of these to calculate an overall Z-score for Planning and Organizing Cognition Measures. Z-scores at baseline and at 12-week follow-up of patients assigned to SSM and HEP will be compared using linear mixed models.

PROTOCOL DEVIATIONS

On March 22, 2019 a protocol deviation occurred when a preliminary analysis (n=14) was completed for the purpose of an undergraduate student research volunteer's course requirements. This volunteer did not have access to patient identifiers. The results were presented at an undergraduate research day as a poster with no abstract in the public domain.

This preliminary analysis has the potential to reduce the available degrees of freedom for the final study analyses. It could also be that blinded personnel (raters and PI) who are now aware of the preliminary results may inadvertently suffer from selection /outcome bias.

The investigators agree that the risk of this preliminary analysis jeopardizing the final analysis is theoretically significant and hence data from these participants will not be included in the final analyses.

On September 5, 2019 two protocol deviations occurred when all the participants in a cohort (n=4) were allocated to attend the SSM intervention. This decision was made at that time a) to maintain recruitment targets and b) to ensure the therapeutic effect of a group intervention a size of 4-6 was felt necessary.

It was felt that that if minimum group size participants are not met, participants will not benefit from the support of their peers as offered by SSM and/or HEP.

As a result of this decision two protocol violations occurred: 1. one participant did not attend the intervention to which they were randomized but rather to the other intervention 2. the study rater was unblinded to the allocations of all 4 participants in this group.

The investigators agree that these protocol deviations will lead to data from these 4 participants to be compromised and hence it will not be analyzed in the final analyses.

Eligibility criteria: Inclusion criteria

1. Patients will be 60-85 years of age presenting with major depressive disorder, single or recurrent, as diagnosed by a Mini Neuropsychiatric Interview (MINI) \[41\].
2. A 17-item Hamilton Depression Rating Scale score of 10-22\[42\].
3. Participants will be willing and able to attend all 4 training sessions of SSM/HEP, as well as 75% of follow-up sessions.
4. Have sufficient hearing to follow verbal instructions;
5. Have adequate understanding of English in London and English and/or French in Montreal.
6. Able to sit for 45 minutes without discomfort.
7. Willing to remain on the same antidepressants including dosage for the first 12 weeks of the study.

Exclusion criteria

1. Inability to independently provide informed consent.
2. Clinical evidence of dementia as defined by Mini-Cog \< 3.a lifetime diagnosis of other mental disorders, including bipolar I or II disorder, primary psychotic disorder (schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder).
3. Substance abuse or dependence within the past 3 months; high risk of suicide (e.g., active suicidal ideation and/or current/recent intent or plan) as assessed by the MINI.
4. Severe personality disorder, that will interfere with their ability to function in a group setting.
5. Substance use disorder as assessed by the MINI.
6. Clinically significant sensory impairment.
7. IQ estimated to be below 70 on the Test of Premorbid Functioning
8. Acutely unstable medical illnesses, including delirium or acute cerebrovascular or cardiovascular events within the last 6 months; having a terminal medical diagnosis with prognosis of less than 12 months.
9. Currently practicing any form of body-mind intervention on a regular basis.

Primary outcomes:
measure: Change in depressive symptoms: Hamilton Depression Scale (HAM-D17)
timeFrame: Change from week 0 to week 12 and change from week 0 to week 26.
Secondary outcomes:
measure: Delis-Kaplan Executive Function System (D-KEFS): Verbal Fluency Test
timeFrame: 0 weeks (baseline); 12 weeks; and 26 weeks
measure: California Verbal Learning Test-II (CVLT-II), Short Form
timeFrame: 0 weeks (baseline); 12 weeks; and 26 weeks
measure: Rey-Osterrieth Complex Figure-Copy Trial
timeFrame: 0 weeks (baseline); 12 weeks; and 26 weeks
Other outcomes:
measure: Generalized Anxiety Disorder 7-item (GAD-7) scale
timeFrame: 0 weeks (at screening or at baseline); 12 weeks; and 26 weeks
measure: Clinical Global Impression (CGI) scale
timeFrame: 0 weeks (baseline); 12 weeks; and 26 weeks
measure: Athens Insomnia Scale
timeFrame: 0 weeks (baseline); 12 weeks; and 26 weeks
measure: World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0)
timeFrame: 0 weeks (baseline); 12 weeks; and 26 weeks
measure: Euroqol 5 Dimension 5 Level (EQ-5D-5L)
timeFrame: 0 weeks (baseline); 12 weeks; and 26 weeks
measure: Toronto Side Effects Scale (TSES)
timeFrame: 0 weeks (baseline); 12 weeks; and 26 weeks
measure: Montreal Cognitive Assessment (MoCA; London only)
timeFrame: 0 weeks (baseline); 12 weeks; and 26 weeks
measure: Wechsler Adult Intelligence Scale (WAIS-IV) -Test of premorbid functioning
timeFrame: 0 weeks (baseline); 12 weeks; and 26 weeks
measure: Wechsler Adult Intelligence Scale (WAIS-IV)-Digit Span
timeFrame: 0 weeks (baseline); 12 weeks; and 26 weeks
measure: Delis-Kaplan Executive Function System (D-KEFS) Color Word Test Conditions 1-3
timeFrame: 0 weeks (baseline); 12 weeks; and 26 weeks
measure: Phenomenology of Consciousness Inventory (PCI)
timeFrame: 12 weeks; and 26 weeks
measure: Ryff Scales of Psychological Well-Being (SPWB)
timeFrame: 0 weeks (baseline); 12 weeks; and 26 weeks
measure: Five Facet Mindfulness Questionnaire (FFMQ)
timeFrame: 0 weeks (baseline); 12 weeks; and 26 weeks
measure: Height
timeFrame: 0 weeks (baseline)
measure: Weight
timeFrame: 0 weeks (baseline); 12 weeks; and 26 weeks
measure: Hip and waist circumference
timeFrame: 0 weeks (baseline); 12 weeks; and 26 weeks
measure: Medications
timeFrame: 0 weeks (baseline); 12 weeks; and 26 weeks
measure: Blood draw
timeFrame: 0 weeks (baseline) and 12 weeks
measure: functional Magnetic Resonance Imaging (fMRI)/Magnetic Resonance Imaging (MRI)/ structural Magnetic Resonance Imaging (sMRI)
timeFrame: 0 weeks (baseline) and 12 weeks
measure: Gait (London only)
timeFrame: 0 weeks (baseline); 12 weeks; and 26 weeks
measure: Fall Efficacy Scale - International (FES-I)
timeFrame: 0 weeks (baseline); 12 weeks; and 26 weeks
measure: Mini-Cog
timeFrame: 0 weeks (screening)
measure: Patient Health Questionnaire (PHQ-9)
timeFrame: 0 weeks (screening), week 12, and week 26.
measure: Antidepressant Treatment History Form (ATHF)
timeFrame: 0 weeks (screening)
measure: Mini International Neuropsychiatric
timeFrame: 0 weeks (screening)
measure: Cumulative Illness Rating Scale - Geriatrics (CIRS-G)
timeFrame: 0 weeks (baseline)
measure: Time Trade Off (TTO)
timeFrame: Weeks 0, week 12, week 24.
measure: Index of Vascular Burden
timeFrame: 0 weeks (baseline)
measure: Socioeconomic Status Index (SES)
timeFrame: 0 weeks (baseline)
measure: Acti watch
timeFrame: Weeks -2 and 14.
measure: Likert Scale
timeFrame: Week 12
measure: Qualitative Side Effects
timeFrame: Weeks 12 and 26.
Locations:
city: London
country: Canada
facility: London Health Sciences Centre
state: Ontario
Study officials:
References:
citation: Peckham SB, Ionson E, Nassim M, Ojha K, Palaniyappan L, Gati J, Theberge J, Lazosky A, Speechley M, Baruss I, Rej S, Vasudev A. Sahaj Samadhi meditation vs a Health Enhancement Program in improving late-life depression severity and executive function: study protocol for a two-site, randomized controlled trial. Trials. 2019 Oct 24;20(1):605. doi: 10.1186/s13063-019-3682-z.