An interventional study of Meditation Training and Waitlist in Prolonged Grief Disorder, sponsored by University Hospital, Caen. Recruiting at 1 site in France. Open to participants aged 18 Years to 60 Years. Per ClinicalTrials.gov, last updated 2025-07-24.
Sponsored by University Hospital, Caen · Not applicable, Interventional, and Treatment
The goal of this clinical trial is to pilot the effectiveness of an 8-week standardized Mindfulness Training program to decrease the psychiatric and somatic symptoms of prolonged grief disorder (PGD) and to examine changes in physiological and neuroimaging biomarkers of bereavement-related stress reactivity that are associated with Mindfulness Training in grieving adult patients (men and women, aged 18-60) who are diagnosed with PGD.
The main questions it aims to answer are:
Participants will be:
Researchers will compare the Mindfulness Training group (which consists of patients with PGD who will receive the Mindfulness Training immediately) with the waitlist control group (which consists of patients with PGD who are waiting on a waitlist to receive the training after the Mindfulness Training group) to investigate if they differ in PGD symptom severity as well as physiological and neuroimaging biomarkers of stress reactivity.
Bereavement is a major life stressor that triggers a stress response that can last months or years after the death of a loved one. This condition of persisting grief response called Prolonged Grief Disorder (PGD) has been recently included in the World Health Organization (WHO) International Classification of Diseases, and the fifth text-revised version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5TR). A core symptom of PGD is the heightened reactivity to reminders of the death. This stress response, if exaggerated and persisting, is associated with increased risk for mental health problems including suicide, as well as somatic problems such as cardiac adverse events. To date, no efficacious intervention for reducing a bereavement-related stress response exist to prevent the negative health outcomes of adults who lost a loved one. Mindfulness Training has shown efficacy to decrease the general stress reactivity, as was shown in healthy individuals and in anxiety disorders, supposedly by improving emotional regulation. Therefore, it has the potential to successfully target bereavement-related stress-reactivity in grievers, as supported by our pilot data. However, it is unknown whether mindfulness meditation may also decrease bereavement-specific stress reactivity, one of the core symptoms of PGD. Furthermore, little is known about the neurobiological changes that underlie the decrease in stress reactivity that results from mindfulness training.
The present proposal is the first ever clinical trial to pilot the effectiveness of an 8-week Mindfulness Training to decrease psychiatric and somatic symptoms of PGD in adult patients, as well as to pilot changes in physiological and neuroimaging biomarkers of bereavement-related stress reactivity that are associated with Mindfulness Training using a script-driven imagery task (which induces bereavement-related stress reactivity during an imagery of a personal situation related to the death compared to imagery of a neutral personal situation), and loud tones stress task (which induces general stress reactivity). As PGD is a newly recognized psychiatric condition, there are very limited data available about its pathophysiology and neurobiology, and in particular how treatments can intervene on it. Although mind-body interventions such as Mindfulness Training have recently shown to be effective for stress-related conditions, limited data are available about their mechanisms of actions. Our proposal is the first to examine trauma-related emotional regulation neural circuits implicated in the effects of Mindfulness Training on pathological grief reactions.
OBJECTIVES:
This study aims to examine the effects of an 8-week standardized Mindfulness Training program on PGD symptom severity and stress reactivity, as well as to elucidate the neural mechanism of these effects, in grieving adult patients who are diagnosed with PGD.
The specific aims of this study are:
Aim 3. Examine potential mechanisms of action of treatment change of Mindfulness Training in a group of patients with PGD who will immediately receive the training versus the waitlist control group.
METHODS:
The investigators conduct a pilot randomized wait-list controlled trial of an 8-week standardized Mindfulness Training program for PGD and examine its effects on physiological and neural correlates of bereavement-related and general stress reactivity. N=30 adults with PGD are included who will be randomly assigned (1:1 group randomization) to immediately receiving an 8-week Mindfulness Training program (experimental group), adapted from the Stress Management and Resiliency Training - SMART, versus after a 12-week waitlist (control group). During a baseline, midpoint, endpoint, and one-month follow-up visit, participants are assessed for psychiatric and somatic symptoms using several questionnaires. In addition, at the baseline and endpoint visit, the investigators will perform functional magnetic resonance imaging (fMRI) to assess functional neuroimaging biomarkers (brain activity and functional connectivity) of bereavement-related and general stress reactivity while collecting physiological responses (heart rate and skin conductance), using a script-driven imagery task (inducing bereavement-related stress reactivity during imagery of a personal situation related to the death versus imagery of a neutral personal situation), and loud tones stress task (inducing general stress reactivity).
Participants will not be blinded to the intervention condition. They will complete self-report questionnaires and be assessed by blinded Independent Evaluators, who will not be involved in the Mindfulness Training sessions, at the baseline (week 0), midpoint (week 4), endpoint (week 8), and follow-up visit (week 12). Participants will be instructed to keep their evaluators blinded to the randomization. Blinded Independent Evaluators will be clinical psychologists who are fully trained in the different measures.
HYPOTHESES:
Hypothesis 2-a. It is hypothesized that adult patients with PGD who are assigned to immediate Mindfulness Training will exhibit significantly greater changes in physiological stress responses, as measured by skin conductance and heart rate,
Hypothesis 2-b. It is hypothesized that adult patients with PGD who are assigned to immediate Mindfulness Training will show significantly greater changes in blood-oxygen-level dependent (BOLD) signals in response to the imagery of a personal situation related to the death (compared to imagery of a neutral personal situation, using a script-driven imagery task) in brain regions that are implicated in emotion regulation and regulatory control at the endpoint visit, compared to the patients in the waitlist control group, including:
PARTICIPATION:
- All potential participants are asked to sign the informed consent form (approved by the ethics committee) with a medical doctor/study clinician prior to participation and are given as much time as needed to review the consent form. The consent form states that participation is voluntary, that participants can refuse to answer any questions, that they can withdraw from the research at any time, and that participation in no way impacts their care. All participants must be beneficiaries of the social security system.
METHODOLOGY
Power considerations:
Our primary analysis follows the intention-to-treat (ITT) principle to compare participants' outcomes according to their initial treatment assignment. The investigators restrict the ITT sample to randomized participants who attend at least one treatment session, including those who do not have analyzable neuroimaging and/or psychophysiological data. With N = 30 participants with usable data for aim 2, and alpha = 0.05 (2-tailed), there will be 80% power to detect a large d=1.1 difference.
Participants may discontinue their participation if they wish, at any time and for any reason, or upon the decision of the investigator.
Premature study exits may be (a) progression of the study condition, (b) participants' refusal to continue, (c) withdrawal of consent, (d) protocol violation requiring a study exit, (e) unblinding, (f) by decision of the investigator, (g) by decision of the sponsor, (h) participant non-compliance.
At every assessment visit, and every 2 weeks during the active phase of the Mindfulness Training, an investigator will assess symptom improvement and worsening, adverse events (reviewed weekly by the Principal Investigator), and suicidal risk assessments (monitored bi-weekly). Any participant at immediate risk, will be referred to a higher level of care and discontinued from the study. A participant is also removed in case of an intercurrent illness, or because they require a new drug or therapeutic method that has demonstrated its efficacy in this indication (in this case, the withdrawal from the trial will occur as soon as the new therapeutic agent is introduced).
Any study withdrawal is documented and specified until the trial exit. The investigators replace each early drop out (over enrollment). Missing data will be handled through maximum likelihood estimation in the primary analysis models, using predictors of missingness and drop-out. The investigators will conduct regular quality checks to maintain data quality throughout. In case of uninterpretable data, they will recruit a few additional participants to reach N=30 with analyzable neuroimaging and psychophysiological data. The investigators anticipate to recruit n=35 total participants to obtain N=30 participants with analyzable neuroimaging and psychophysiological data (anticipated dropout = 20%).
CONSIDERATIONS AND OBLIGATIONS:
39 studies on the registry are indexed under Prolonged Grief Disorder; 14 are open to participants now.
This study's planned enrollment of 30 is below the median of 68 across 35 interventional studies indexed under Prolonged Grief Disorder.
Browse Prolonged Grief Disorder studies →University Hospital, Caen is the lead sponsor of 505 studies on the registry; 80 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
The Immediate Meditation Training group will immediately receive 8 weekly sessions of Mindfulness Training within 4 weeks after the Baseline visit (V0, during which participants are randomized).
Behavioral: Meditation Training
The Waitlist Control group will receive the Mindfulness Training after a waiting time of 12 weeks. Participants in this group will not receive any type of intervention before this and will wait till the Immediate Meditation Training group finished all assessment visits (including the follow-up visit in week 12 (V3)).
Behavioral: Waitlist
The Meditation Training consists of 8 weekly sessions of Mindfulness Training and is adapted from the group-based Stress Management and Resiliency Training - Relaxation Response Resiliency Program, SMART-3RP. This training is structured around the following four goals: 1. Education about stress response 2. Elicitation of the Relaxation Response through Mindfulness Training 3. Creating adaptive perspectives 4. Coping strategiest.
Also known as: Mindfulness Training, SMART
The waitlist consists of a waiting time of 12 weeks during which participants will nog receive any type of intervention.
Mean change in Prolonged Grief Disorder (PGD) symptom severity from the pre-intervention baseline to the post-intervention endpoint visit.
PGD symptom severity is assessed by the Inventory of Complicated Grief (ICG) questionnaire.
Time frame: Assessed during the pre-intervention baseline (week 0), post-intervention endpoint (week 8), and one-month follow-up visit (week 12).
Mean change in Prolonged Grief Disorder (PGD) symptom severity from the pre-intervention baseline to the post-intervention endpoint, and one-month follow-up visit.
PGD symptom severity is assessed by the Structural Clinical Interview for Complicated Grief (SCI-CG).
Time frame: Assessed during the pre-intervention baseline (week 0), post-intervention endpoint (week 8), and one-month follow-up visit (week 12).
Mean change in Posttraumatic Stress Disorder (PTSD) symptom severity in relation to the death, from the pre-intervention baseline to the post-intervention endpoint, and one-month follow-up visit.
PTSD symptom severity is assessed by the PTSD Checklist for DSM-5 (PCL-5).
Time frame: Assessed during the pre-intervention baseline (week 0), post-intervention endpoint (week 8), and one-month follow-up visit (week 12).
Mean change in Depression symptom severity from the pre-intervention baseline to the post-intervention endpoint, and one-month follow-up visit.
Depression symptom severity is assessed by the Quick Inventory of Depressive Symptomatology (QIDS-SR).
Time frame: Assessed during the pre-intervention baseline (week 0), post-intervention endpoint (week 8), and one-month follow-up visit (week 12).
Mean change in somatic complaints from the pre-intervention baseline to the post-intervention endpoint, and one-month follow-up visit.
Somatic symptoms are assessed by the Medical Symptom Checklist (MSCL).
Time frame: Assessed during the pre-intervention baseline (week 0), post-intervention endpoint (week 8), and one-month follow-up visit (week 12).
Mean change in the ability to cope with stress from the pre-intervention baseline to the post-intervention endpoint, and one-month follow-up visit.
Coping ability with stress is assessed by the Measure of Current Status (MOCS).
Time frame: Assessed during the pre-intervention baseline (week 0), post-intervention endpoint (week 8), and one-month follow-up visit (week 12).
Mean change in global symptom severity from the pre-intervention baseline to the post-intervention endpoint, and one-month follow-up visit.
Global symptom severity is assessed by the Clinical Global Impressions of Severity scale (CGI-S).
Time frame: Assessed during the pre-intervention baseline (week 0), post-intervention endpoint (week 8), and one-month follow-up visit (week 12).
Mean change in global symptom improvement from the mid-intervention midpoint to the post-intervention endpoint, and one-month follow-up visit.
Global symptom improvement is assessed by the Clinical Global Impressions of Improvement scale (CGI-I).
Time frame: Assessed during the mid-intervention midpoint (week 4), post-intervention endpoint (week 8), and one-month follow-up visit (week 12).
Mean change in skin conductance response rates to bereavement-related stress from the pre-intervention baseline to the post-intervention endpoint visit.
Skin conductance response rates during the Script-Driven Imagery paradigm are measured as peripheral biomarkers of bereavement-related stress reactivity in the neuroimaging scanner.
Time frame: Assessed during the pre-intervention baseline (week 0) and post-intervention endpoint visit (week 8).
Mean change in heart rate responses to bereavement-related stress from the pre-intervention baseline to the post-intervention endpoint visit.
Heart rate responses during the Script-Driven Imagery paradigm are measured as peripheral biomarkers of bereavement-related stress reactivity in the neuroimaging scanner.
Time frame: Assessed during the pre-intervention baseline (week 0) and post-intervention endpoint visit (week 8).
Mean change in skin conductance response rates during general stress from the pre-intervention baseline to the post-intervention endpoint visit.
Skin conductance response rates during the Loud Tones paradigm are measured as peripheral biomarkers of general stress reactivity in the neuroimaging scanner.
Time frame: Assessed during the pre-intervention baseline (week 0) and post-intervention endpoint visit (week 8).
Mean change in heart rate responses to general stress from the pre-intervention baseline to the post-intervention endpoint visit.
Heart rate responses during the Loud Tones paradigm are measured as peripheral biomarkers of general stress reactivity in the neuroimaging scanner.
Time frame: Assessed during the pre-intervention baseline (week 0) and post-intervention endpoint visit (week 8).
Mean change in Blood Oxygentation Level Dependent (BOLD brain activity) signals during bereavement-related stress from the pre-intervention baseline to the post-intervention endpoint visit.
Blood Oxygentation Level Dependent (BOLD brain activity) signals during a Script-Driven Imagery paradigm are measured as neural biomarkers of bereavement-related stress reactivity in the neuroimaging scanner.
Time frame: Assessed during the pre-intervention baseline (week 0) and post-intervention endpoint visit (week 8).
Mean change in brain Functional Connectivity during bereavement-related stress from the pre-intervention baseline to the post-intervention endpoint visit.
Brain Functional Connectivity during a Script-Driven Imagery paradigm are measured as neural biomarkers of bereavement-related stress reactivity in the neuroimaging scanner.
Time frame: Assessed during the pre-intervention baseline (week 0) and post-intervention endpoint visit (week 8).
Mean change in Blood Oxygentation Level Dependent (BOLD brain activity) signals during general stress from the pre-intervention baseline to the post-intervention endpoint visit.
Blood Oxygentation Level Dependent (brain activity) signals during a Loud Tones paradigm are measured as neural biomarkers of general stress reactivity in the neuroimaging scanner.
Time frame: Assessed during the pre-intervention baseline (week 0) and post-intervention endpoint visit (week 8).
Mean change in brain Functional Connectivity during general stress from the pre-intervention baseline to the post-intervention endpoint visit.
Brain Functional Connectivity during a Loud Tones paradigm are measured as neural biomarkers of general stress reactivity in the neuroimaging scanner.
Time frame: Assessed during the pre-intervention baseline (week 0) and post-intervention endpoint visit (week 8).
Characteristics of the death.
Charcteristics of the death are assessed as covariates and include the time since the loss, the type of death, the cause of death, and the relationship between the participant and the deceased.
Time frame: Assessed during the screening visit (week-4 until 0).
The absence of diagnostic exclusion criteria and co-occurring Axis-I psychiatric disorders.
Diagnoses is assessed by the Mini International Neuropsychiatric Interview (MINI).
Time frame: Assessed during the screening visit (week-4 until 0).
Socio-demographic variables.
Socio-demographic variables are assessed as potential Confounders for grief reactions and include age, sex, gender, socioeconomic status, educational level, racial and ethnic origins, menstrual cycle information, and handedness.
Time frame: Assessed during the screening visit (week-4 until 0).
Self-reports of mood and bereavement-related stress responses.
Self-report mood and bereavement-related stress responses measured on 8-point Likert scales (range 0 "none" - 8 "a great deal") are assessed for vividness, valence related to control/dominance, happiness/pleasure, and excitement/ arousal of their imagery, as well as feelings of sadness, anger, fear, disgust, surprise, guilt, emotional pain and yearning for the deceased during each imagery phase of the Script-Driven Imagery paradigm in the neuroimaging scanner to check that the paradigm elicited the intended emotions.
Time frame: Assessed during each imagery phase of the Script-Driven Imagery paradigm during the pre-intervention baseline (week 0) and post-intervention endpoint visit (week 8).
Mean change in self-reports of mood and bereavement-related stress responses from the pre-intervention baseline to the post-intervention endpoint visit.
Self-report mood and bereavement-related stress responses measured on 8-point Likert scales (range 0 "none" - 8 "a great deal") are assessed for vividness, valence related to control/dominance, happiness/pleasure, and excitement/ arousal of their imagery, as well as feelings of sadness, anger, fear, disgust, surprise, guilt, emotional pain and yearning for the deceased during each imagery phase of the Script-Driven Imagery paradigm in the neuroimaging scanner.
Time frame: Assessed during each imagery phase of the Script-Driven Imagery paradigm, and from the pre-intervention baseline (week 0) to post-intervention endpoint visit (week 8).
Procedure-related time variables.
Procedure-related time variables are assessed as potential potential covariates and include time of arrival and end time during assessment visits.
Time frame: Assessed during the screening visit (week -4 until 0), baseline visit (week 0), midpoint visit (week 4), endpoint visit (week 8), follow-up visit (week 12), and 2-weekly safety checks (week 2, week 6).
Potential adverse events experienced by the participant.
Potential adverse events are assessed as safety check-in assessment using the Adverse Events Monitoring Form.
Time frame: Assessed during the screening visit (week -4 until 0), baseline visit (week 0), midpoint visit (week 4), endpoint visit (week 8), follow-up visit (week 12), and 2-weekly safety checks (week 2, week 6).
Suicidal risk experienced by the participant.
Suicidal risk is assessed as safety check-in assessment and will include the severity of a patient's suicidal ideation using the Clinician Suicide Assessment Checklist (CSAS).
Time frame: Assessed during the screening visit (week -4 until 0), baseline visit (week 0), midpoint visit (week 4), endpoint visit (week 8), follow-up visit (week 12), and 2-weekly safety checks (week 2, week 6).
Procedure-related comments
Procedure-related comments are assessed as any important notes or comments about the research procedures.
Time frame: Assessed during the screening visit (week -4 until 0), baseline visit (week 0), midpoint visit (week 4), endpoint visit (week 8), follow-up visit (week 12), and 2-weekly safety checks (week 2, week 6).
Plan to share: No
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