Mechanisms of Mindfulness-based Interventions | NCT03571386

NCT03571386

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Description Module

Detailed Description

The state of mindfulness can be described as a form of meta-awareness in which attention is allocated to the present moment of external and internal sensory or mental experience, without reactivity, and without dwelling on any particular sensory or mental object with judgement or evaluation. Mindfulness-based Interventions (MBIs) are a family of standardized cognitive and behavioral therapies that focus on cultivating mindfulness-related skills for improving maladaptive cognitive, emotional, and behavioral processes.

MBIs have been developed for a wide range of problems, disorders, and populations and are increasingly available in a variety of health settings. Empirically supported MBIs include acceptance and commitment therapy (ACT; Hayes, Strosahl, & Wilson, 1999), dialectical behavior therapy (DBT; Linehan, 1993), mindfulness-based cognitive therapy (MBCT; Segal, Williams, & Teasdale, 2002), and mindfulness-based stress reduction (MBSR; Kabat-Zinn, 1982, 1990). Variations on these approaches, including integration of mindfulness training into individual psychotherapy from diverse perspectives, also have been described (Germer, Siegel, & Fulton, 2005). As the empirical evidence for the efficacy of these interventions continues to grow, the importance of investigating the mechanisms or processes by which they lead to beneficial outcomes is increasingly recognized. This mixed methods study proposes to investigate proposed neurobiological, physiological, psycho-social-behavioral, and cognitive mechanisms by which MBIs may improve health outcomes. Target (mechanism) engagement is expected to facilitate identification of individuals who are most likely to benefit (or not) from MBIs and further develop targeted interventions for optimization of delivery. Although there are very specific aims and hypotheses to be tested, this preliminary exploratory investigation will provide feasibility data and allow for refining existing hypotheses for larger research proposals to be submitted for extramural grant support.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Mild to Moderate Depression and/or Anxiety		Patients who currently have mild to moderate severity of depression and/or anxiety symptoms are who are receiving Mindfulness-Based Cognitive Therapy (MBCT) in a group setting as standard of care will be recruited for this arm.	Behavioral: Mindfulness-based Cognitive Therapy (MBCT)
High Stress		Patients with a history of reported stress who are receiving Mindfulness-Based Stress Reduction (MBSR) in a group setting as standard of care will be recruited for this study. All patients are eligible.	Behavioral: Mindfulness-based Stress Reduction (MBSR)

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Mindfulness-based Cognitive Therapy (MBCT)	Behavioral	Standardized 8-week Cognitive and Behavioral Psychotherapy group with 26 hrs of in-class training and homework, along with 1 all-day retreat in which core mindfulness skills are developed

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change in BOLD (Blood-oxygen-level-dependent) Mean Signal Change From Baseline to 12 Weeks in Response to Emotional (vs. Neutral) Word Stimuli	fMRI BOLD response to emotional word stimuli baseline to 12 weeks (post-MBCT). BOLD signal change (pre- to post-MBCT) is estimated from the contrast of emotional word vs neutral words, and extracted from voxels within the fronto-parietal and default mode areas at baseline and 12-weeks. Significant Voxel-wise BOLD activity is reported using z-scores from peak voxels. A mean score was calculated based on z-score and SD of 2 in the context of reporting fMRI BOLD data here. Z-scores is a statistical measure that describes how many standard deviations a data point (e.g., a voxel's signal) is from the mean of the distribution of that signal. The higher the reported mean, the less likely the observed activation is due to chance, thus indicating more significant activity or activation in that particular brain region.	Baseline to 12 weeks

Secondary Outcomes

Measure	Description	Time Frame
Amplitude of P1 Event-related Potentials (ERP) in Response to Threat (vs. Neutral) Face Cues Pre- to Post-MBCT	P1 Evoked event-related electrical potentials (ERP) amplitudes elicited from specific emotional threat vs. neutral stimuli were primary outcome. An 80-150 ms search window at EEG electrode P8 was used to identify the P1 peak, & mean value around peaks (50 ms) was exported for analysis. Mean P1-Cue amplitudes were analyzed pre- to post-MBCT to determine the effects of time (pre to post-MBCT), emotion (angry vs. happy), and congruency (congruent vs. incongruent). Mean P1-Cue amplitudes in microvolts and SD for each condition are summarized below.

Other Outcomes

Measure	Description	Time Frame
Self-report Psychological Measures of Anxiety and Stress Pre- to Post-Mindfulness Training	The Depression & Anxiety Stress Scale (DASS-Anxiety) (Lovibond and Lovibond, 1995) is a 7-item measure designed to assess symptoms of fear and autonomic arousal. Items are rated on a 4-point scale, ranging from 0 (did not apply to me at all) to 3 (applied to me very much or most of the time), and summed to compute the total scale (range 0-21). Higher scores are indicative of greater symptom severity, with scores greater than 10 typically considered of clinical significance. The DASS-Depression is a 7-item measure designed to assess dysphoric mood. Items are rated on a 4-point Likert scale, ranging from 0 (did not apply to me at all) to 3 (applied to me very much or most of the time), and summed to compute the total scale (range 0-21). Higher scores are indicative of greater symptom severity, with scores greater than 10 typically considered of clinical significance.

Eligibility Module

Eligibility Criteria

Across all ARMS:

At prescreen, must be currently registered for MBCT or MBSR; at posttest, must have attended five of eight sessions for "completion".
Must possess English language skills sufficient for providing informed consent, completing questionnaires, and understanding instructions
Age range: 18-55
Right-handed
If currently taking maintenance anti-depressant and/or anti-anxiety medication, must have a "stable" regimen as indexed by no medication or dosage changes within the past three months
No prior diagnosis of bipolar I, bipolar II, psychotic personality disorder, borderline personality disorder, and/or narcissistic personality disorder
No current history (< 6 months) of substance abuse/dependence
No current history (< 6 months) of regular meditation practice (>1 session/week; >10 min/session)
No history of medical illness associated with possible changes in cerebral tissue or cerebrovasculature or with neurologic abnormality (e.g., seizure disorder, cerebrovascular or neoplastic lesion, neurodegenerative disorder, or significant head trauma, defined by loss of consciousness of ≥ 5 minutes)
No current suicidal ideation

Eligibility for Depression & Anxiety Cohort:

Depression

Reports having been diagnosed with non-psychotic unipolar major depressive disorder (MDD)
≥3 previous episodes of MDD
Beck Depression Inventory-II (BDI-II) score between 14 and 28 (an indicator of depressive symptoms of mild to moderate severity)
No fMRI contraindications: pregnancy, claustrophobia, or presence of a ferromagnetic object, including orthodontic braces

Anxiety:

Reports having been diagnosed with an anxiety disorder (i.e., generalized anxiety disorder, panic disorder, specific phobia)
Score of ≥40 on the Trait subscale of the Spielberger State-Trait Anxiety Inventory (an indicator of anxious symptoms of moderate to high severity)

Eligibility for High Stress Cohort:

- Reports of High Stress as measured by perceived Stress Scale

Eligibility for Drawing Blood:

At least 110 pounds
Not pregnant
Generally healthy by self-report (i.e., free of cold and flu symptoms on the day of collection, no infections within two weeks prior to collection, no symptoms of a heart condition within six months prior to collection, no known sickle cell disease)
Including the study draw, blood donation for clinical or research purposes within the preceding eight weeks will not exceed 550 mL
No more than one blood draw will have occurred during the preceding week

Name	Affiliation	Role
David R Vago, Ph.D.	Vanderbilt University Medical Center	Principal Investigator
Poppy Schoenberg, Ph.D.	Vanderbilt University Medical Center	Principal Investigator
Resh Gupta, Ph.D.	University of California, San Diego	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Vanderbilt University Medical Center		Nashville	Tennessee	37232	United States

PubMed Identifier	Type	Citation	Retractions
31605728	Background	Gupta RS, Kujawa A, Vago DR. The neural chronometry of threat-related attentional bias: Event-related potential (ERP) evidence for early and late stages of selective attentional processing. Int J Psychophysiol. 2019 Dec;146:20-42. doi: 10.1016/j.ijpsycho.2019.08.006. Epub 2019 Oct 9.
30682701	Background

Arm/Group Information

ID	Title	Description
FG000	Mild to Moderate Depression and/or Anxiety	Patients who currently have mild to moderate severity of depression and/or anxiety symptoms are who are receiving Mindfulness-Based Cognitive Therapy (MBCT) in a group setting as standard of care will be recruited for this arm. Mindfulness-based Cognitive Therapy (MBCT): Standardized 8-week Cognitive and Behavioral Psychotherapy group with 26 hrs of in-class training and homework, along with 1 all-day retreat in which core mindfulness skills are developed
FG001	High Stress	Patients with a history of reported stress who are receiving Mindfulness-Based Stress Reduction (MBSR) in a group setting as standard of care will be recruited for this study. All patients are eligible. Mindfulness-based Stress Reduction (MBSR): Standardized 8-week patient-centered educational approach which uses relatively intensive training in core meditation practices that teaches people how to take better care of themselves using mindfulness skills and live healthier and more adaptive lives.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Mild to Moderate Depression and/or Anxiety	Patients who currently have mild to moderate severity of depression and/or anxiety symptoms are who are receiving Mindfulness-Based Cognitive Therapy (MBCT) in a group setting as standard of care will be recruited for this arm. Mindfulness-based Cognitive Therapy (MBCT): Standardized 8-week Cognitive and Behavioral Psychotherapy group with 26 hrs of in-class training and homework, along with 1 all-day retreat in which core mindfulness skills are developed

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type	Title	Description	Population Description	Reporting Status	Anticipated Posting Date	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Time Frame	Units Analyzed	Denominator Units Selected	Arm/Group Information	Denominators	Classes	Analyses
Primary	Change in BOLD (Blood-oxygen-level-dependent) Mean Signal Change From Baseline to 12 Weeks in Response to Emotional (vs. Neutral) Word Stimuli	fMRI BOLD response to emotional word stimuli baseline to 12 weeks (post-MBCT). BOLD signal change (pre- to post-MBCT) is estimated from the contrast of emotional word vs neutral words, and extracted from voxels within the fronto-parietal and default mode areas at baseline and 12-weeks. Significant Voxel-wise BOLD activity is reported using z-scores from peak voxels. A mean score was calculated based on z-score and SD of 2 in the context of reporting fMRI BOLD data here. Z-scores is a statistical measure that describes how many standard deviations a data point (e.g., a voxel's signal) is from the mean of the distribution of that signal. The higher the reported mean, the less likely the observed activation is due to chance, thus indicating more significant activity or activation in that particular brain region.	Only 16 participants in Mild to moderate depression and/or anxiety participated in fMRI data collection. Participants in the "High Stress" Arm/Group were not assessed using fMRI and the subgroup was smaller given financial constraints.	Posted		Mean	Standard Error	units on a scale		Baseline to 12 weeks

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Mild to Moderate Depression and/or Anxiety	Patients who currently have mild to moderate severity of depression and/or anxiety symptoms are who are receiving Mindfulness-Based Cognitive Therapy (MBCT) in a group setting as standard of care will be recruited for this arm. Mindfulness-based Cognitive Therapy (MBCT): Standardized 8-week Cognitive and Behavioral Psychotherapy group with 26 hrs of in-class training and homework, along with 1 all-day retreat in which core mindfulness skills are developed

Title	Organization	Phone	Extension	Email
David Vago	Vanderbilt University	236-516-6530		vago.dave@gmail.com

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Aug 28, 2019	Jun 28, 2022	Prot_SAP_000.pdf
ICF	No	No	Yes	Informed Consent Form	Aug 9, 2021	Jun 28, 2022	ICF_001.pdf

ID	Term
D003863	Depression
D001008	Anxiety Disorders

ID	Term
D001526	Behavioral Symptoms
D001519	Behavior
D001523	Mental Disorders

ID	Term
D000099025	Mindfulness-Based Cognitive Therapy
D000099024	Mindfulness-Based Stress Reduction

ID	Term
D064866	Mindfulness
D015928	Cognitive Behavioral Therapy
D001521	Behavior Therapy
D011613	Psychotherapy

ID	Title	Description
OG000	Mild to Moderate Depression and/or Anxiety	Patients who currently have mild to moderate severity of depression and/or anxiety symptoms are who are receiving Mindfulness-Based Cognitive Therapy (MBCT) in a group setting as standard of care will be recruited for this arm. Mindfulness-based Cognitive Therapy (MBCT): Standardized 8-week Cognitive and Behavioral Psychotherapy group with 26 hrs of in-class training and homework, along with 1 all-day retreat in which core mindfulness skills are developed
OG001	High Stress	Patients with a history of reported stress who are receiving Mindfulness-Based Stress Reduction (MBSR) in a group setting as standard of care will be recruited for this study. All patients are eligible. Mindfulness-based Stress Reduction (MBSR): Standardized 8-week patient-centered educational approach which uses relatively intensive training in core meditation practices that teaches people how to take better care of themselves using mindfulness skills and live healthier and more adaptive lives.