Loving-Kindness Meditation for PTSD

• Sponsor: VA Office of Research and Development (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT01962714
• Collaborator: (none)
• Enrollment: 184
• Location: 1
• Arms: 2
• Actual Duration (Months): 47.9
• Patients Per Site Per Month: 3.8

Study Details

Study Description

Brief Summary

This randomized controlled trial will assess whether a novel complementary and alternative medicines (CAM) intervention, Loving-kindness Meditation (LKM), is not meaningfully inferior to another group-based PTSD treatment , Cognitive Processing Therapy (Cognitive Only version; CPT-C) for reductions in PTSD and depressive symptoms. 170 male and female Veterans with current PTSD will be randomized to LKM or CPT-C. The investigators hypothesize that Veterans randomized to LKM will report mean reductions in PTSD and depressive symptom severity that are not meaningfully worse than CPT-C. The investigators further hypothesize that reductions in posttraumatic maladaptive beliefs will more strongly mediate PTSD and depressive symptom improvement for those assigned to CPT-C than those assigned to LKM.

Condition or Disease	Intervention/Treatment	Phase
Posttraumatic Stress Disorder; Depression	Behavioral: Loving-Kindness Meditation; Behavioral: Cognitive Processing Therapy	N/A

Detailed Description

Aim 1: Evaluate if LKM is non-inferior to CPT-C in producing reductions in PTSD symptoms among Veterans with current PTSD. Aim 2: Evaluate the non-inferiority of LKM and CPT-C in producing reductions in depressive symptoms among Veterans with current PTSD. Exploratory Aim: Evaluate potential mediators of response to LKM and to CPT to provide preliminary information regarding whether they are consistent with the mechanisms of change conceptualized by each intervention to be associated with improvement in PTSD and depression.

Methods: A randomized controlled non-inferiority trial comparing LKM to CPT-C. In the proposed project 170 Veterans with PTSD will be randomized to LKM or CPT-C. Comprehensive assessments will be performed at baseline as well as at the end of the 12-week interventions and 3 and 6 months later. PTSD symptoms, depression, posttraumatic maladaptive cognitions and self-compassion will be assessed weekly during the treatment phase to assess temporality of change and to assess mediators of outcomes.

Study Design

• Study Type: Interventional
• Actual Enrollment: 184 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Trial of Loving-Kindness Meditation and Cognitive Processing Therapy for PTSD
• Actual Study Start Date: Dec 1, 2014
• Actual Primary Completion Date: Nov 29, 2018
• Actual Study Completion Date: Nov 29, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Loving-Kindness Meditation A 12-week duration, 90-minute per session Loving-Kindness Meditation (LKM) course, taught in groups of 10 participants.	Behavioral: Loving-Kindness Meditation; 12-week loving-kindness meditation course
Active Comparator: Cognitive Processing Therapy - Cognitive Only A 12-week duration, 90-minute per session Cognitive Processing Therapy (CPT) course, taught in groups of 10 participants.	Behavioral: Cognitive Processing Therapy; 12-week CPT course

Outcome Measures

Primary Outcome Measures

1. Clinician Administered PTSD Scale (CAPS-5) Score [6 months post-intervention]

   PTSD diagnostic severity was measured using the 30-item CAPS-5 structured interview (range 0-80; higher scores indicate worse PTSD). Linear mixed effects models (LMM) were used to analyze continuous outcomes, with time and time by treatment interaction included as fixed effects to determine if differences exist between conditions by time. Non-inferiority of LKM to CPT-C was claimed if the lower limit of the 95% confidence interval for difference in change rate from baseline to 6-month follow-up in mean CAPS or depression score was greater than (i.e., did not extend beyond) negative delta (defined as 5 points on the CAPS-5 measure). A 2-sided 95% confidence interval of the difference in change rate from baseline to 6-month follow-up between groups (CPT-C minus LKM) was calculated, with a positive value indicating a greater reduction in scores from baseline for LKM compared to CPT-C.

2. NIH Patient-Reported Outcomes Measurement Information System (PROMIS) Depression Score [6 months post-intervention]

   Depression was assessed using the National Institute of Health (NIH) Patient-Reported Outcomes Measurement Information System (PROMIS) depression measure. This scale utilizes item-response theory and is scored using a T-score metric with a mean of 50 and SD=10 in the US general population. Higher scores indicate more severe depression.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Current Diagnostic and Statistical Manual of Mental Disorder (DSM)-5 diagnosis of PTSD,

• 18 or over,

• English fluency,

• Willingness to not participate in Mindfulness-Based Stress Reduction or other meditation programs, as well as Prolonged Exposure (PE) or CPT during the study period.

Exclusion Criteria:

• Any of the following substance use criteria: 1) Use in the past 90 days of illicit substance (do not include cannabis)/ street drug (non-prescribed); 2) Use in the past 90 days of prescription drug of abuse, use is not as prescribed AND poses safety concern

• Alcohol involvement that poses a safety concern or is associated with inability to follow through on assessments and class attendance as evinced by current drinking AND dt's or seizure in past year

• Suicidal or homicidal ideation with intent or plan

• Attempted harm to Self or others in the past month

• A lifetime psychotic disorder or current psychotic symptoms

• Uncontrolled bipolar disorder (ie current mania, current hypomania is not an exclusion)

• Chart diagnoses of borderline personality disorder or antisocial personality disorder

• In-patient admission for psychiatric reasons within the past month

• Prior participation in LKM or CPT

• Dementia

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA Puget Sound Health Care System Seattle Division, Seattle, WA	Seattle	Washington	United States	98108

Sponsors and Collaborators

• VA Office of Research and Development

Investigators

• Principal Investigator: David J. Kearney, MD, VA Puget Sound Health Care System Seattle Division, Seattle, WA

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 31, 2014

More Information

Publications

None provided.

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT01962714
• Other Study ID Numbers: MHBA-006-13S; 5I01CX000857-02
• First Posted: Oct 14, 2013
• Last Update Posted: Mar 17, 2020
• Last Verified: Mar 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by VA Office of Research and Development: Behavior therapies, cognitive; Mindfulness; Emotion; Group therapy
• Additional relevant MeSH terms: Stress Disorders, Post-Traumatic

Study Results

Participant Flow

Arm/Group Title	Loving-Kindness Meditation	Cognitive Processing Therapy - Cognitive Only
Arm/Group Description	A 12-week duration, 90-minute per session Loving-Kindness Meditation (LKM) course, taught in groups of 10 participants. Loving-Kindness Meditation: 12-week loving-kindness meditation course	A 12-week duration, 90-minute per session Cognitive Processing Therapy (CPT) course, taught in groups of 10 participants. Cognitive Processing Therapy: 12-week CPT course
Period Title: Overall Study
STARTED	91	93
Immediate Post-treatment Assessment	63	57
3-month Follow-up	58	56
COMPLETED	61	60
NOT COMPLETED	30	33

Baseline Characteristics

Arm/Group Title	Loving-Kindness Meditation	Cognitive Processing Therapy - Cognitive Only	Total
Arm/Group Description	The intervention consisted of 12 weekly 90-minute group sessions. In Loving-Kindness Meditation, a person sits and calls to mind a particular person (e.g., a good friend) and silently repeats phrases that invoke goodwill for that person, e.g., the desire for safety, happiness, health, and peace. Over 12 weeks, the practice expands to bring to mind other individuals or categories of people, including themselves, neutral persons, and those who have caused difficulty or harm, changing the phrases as needed. Participants are asked to notice any thoughts and feelings elicited by the phrases with an attitude of kindness, curiosity, and non-judgment, regardless of content. Each session begins with either mindfulness meditation (weeks 1 & 2) or LKM meditation (weeks 3 through 12) followed by group discussion and additional LKM teaching and practice. Homework for LKM consisted of 30 minutes of meditation 6 days per week using compact disks (CDs) as well as informal LKM practice in daily life.	CPT-C does not include writing a trauma narrative. The intervention is based on Resick and colleagues' manual for treating PTSD among military veterans, which combines cognitive restructuring with emotional processing of trauma- related content. Sessions initially focus on rigid or inaccurate beliefs about the traumatic event itself, which often reflect self-blame or hindsight bias. Later sessions address over-generalized beliefs about self and others that result from a traumatic event relevant to five key areas: safety, trust, power, esteem, and intimacy. Clients learn to identify and modify their beliefs to develop more balanced, flexible, and ultimately, more adaptive beliefs. Homework for CPT-C consisted of 30 minutes of homework 6 days a week, including writing an impact statement at the beginning and the end of treatment and completing worksheets and exercises regarding safety, trust, power/control, esteem, and intimacy.	Total of all reporting groups
Overall Participants	91	93	184
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.2 (12.5)	56.1 (13.7)	57.1 (13.1)
Sex/Gender, Customized (Count of Participants)
Male	77 84.6%	76 81.7%	153 83.2%
Female	13 14.3%	17 18.3%	30 16.3%
Transgender	1 1.1%	0 0%	1 0.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 3.3%	6 6.5%	9 4.9%
Not Hispanic or Latino	88 96.7%	87 93.5%	175 95.1%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	3 3.2%	3 1.6%
Asian	3 3.3%	3 3.2%	6 3.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	24 26.4%	20 21.5%	44 23.9%
White	53 58.2%	54 58.1%	107 58.2%
More than one race	11 12.1%	12 12.9%	23 12.5%
Unknown or Not Reported	0 0%	1 1.1%	1 0.5%
Region of Enrollment (Count of Participants)
United States	91 100%	93 100%	184 100%
Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual (DSM)-5 (CAPS-5) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	35.54 (12.12)	35.53 (11.48)	35.53 (11.77)

Outcome Measures

1. Primary Outcome

Title	Clinician Administered PTSD Scale (CAPS-5) Score
Description	PTSD diagnostic severity was measured using the 30-item CAPS-5 structured interview (range 0-80; higher scores indicate worse PTSD). Linear mixed effects models (LMM) were used to analyze continuous outcomes, with time and time by treatment interaction included as fixed effects to determine if differences exist between conditions by time. Non-inferiority of LKM to CPT-C was claimed if the lower limit of the 95% confidence interval for difference in change rate from baseline to 6-month follow-up in mean CAPS or depression score was greater than (i.e., did not extend beyond) negative delta (defined as 5 points on the CAPS-5 measure). A 2-sided 95% confidence interval of the difference in change rate from baseline to 6-month follow-up between groups (CPT-C minus LKM) was calculated, with a positive value indicating a greater reduction in scores from baseline for LKM compared to CPT-C.
Time Frame	6 months post-intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Loving-Kindness Meditation	Cognitive Processing Therapy - Cognitive Only
Arm/Group Description	A 12-week duration, 90-minute per session Loving-Kindness Meditation (LKM) course, taught in groups of 10 participants. Loving-Kindness Meditation: 12-week loving-kindness meditation course	A 12-week duration, 90-minute per session Cognitive Processing Therapy (CPT) course, taught in groups of 10 participants. Cognitive Processing Therapy: 12-week CPT course
Measure Participants	91	93
Mean (95% Confidence Interval) [units on a scale]	25.92	28.02

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Loving-Kindness Meditation, Cognitive Processing Therapy - Cognitive Only
	Comments	The non-inferiority of LKM with respect to CPT-C was analyzed using the 95% confidence interval for the group x time interaction term, with non-inferiority of LKM to CPT-C claimed if the lower limit of the 95% confidence interval was greater than (i.e., did not extend beyond) negative delta.
	Type of Statistical Test	Non-Inferiority
	Comments	The primary outcome of non-inferiority of LKM relative to CPT-C was assessed using a non-inferiority margin of 5 points on the CAPS-5, which represents 0.5 SD of baseline PTSD symptoms based on data indicating the SD of baseline CAPS-5 scores is approximately 10 in a large sample (N=198) of treatment-seeking veterans.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.09
	Confidence Interval	(2-Sided) 95%; -2.59 to 6.78
	Parameter Dispersion	Type: Value:
	Estimation Comments	Non-inferiority of LKM to CPT-C was analyzed as the change rate from baseline to 6-month follow-up between groups (CPT-C minus LKM), with a positive value indicating a greater reduction in scores for LKM compared to CPT-C.

2. Primary Outcome

Title	NIH Patient-Reported Outcomes Measurement Information System (PROMIS) Depression Score
Description	Depression was assessed using the National Institute of Health (NIH) Patient-Reported Outcomes Measurement Information System (PROMIS) depression measure. This scale utilizes item-response theory and is scored using a T-score metric with a mean of 50 and SD=10 in the US general population. Higher scores indicate more severe depression.
Time Frame	6 months post-intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Loving-Kindness Meditation	Cognitive Processing Therapy - Cognitive Only
Arm/Group Description	A 12-week duration, 90-minute per session Loving-Kindness Meditation (LKM) course, taught in groups of 10 participants. Loving-Kindness Meditation: 12-week loving-kindness meditation course	A 12-week duration, 90-minute per session Cognitive Processing Therapy (CPT) course, taught in groups of 10 participants. Cognitive Processing Therapy: 12-week CPT course
Measure Participants	91	93
Mean (95% Confidence Interval) [units on a scale]	58.88	61.22

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Loving-Kindness Meditation, Cognitive Processing Therapy - Cognitive Only
	Comments	The non-inferiority of LKM with respect to CPT-C was analyzed using the 95% confidence interval for the group x time interaction term, with non-inferiority of LKM to CPT-C claimed if the lower limit of the 95% confidence interval was greater than (i.e., did not extend beyond) negative delta.
	Type of Statistical Test	Non-Inferiority
	Comments	For depression, the non-inferiority margin was 4 points on the PROMIS depression measure, which has been defined as the minimally important difference and corresponds to a Cohen's d effect size of approximately 0.50.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.34
	Confidence Interval	(2-Sided) 95%; -0.52 to 5.20
	Parameter Dispersion	Type: Value:
	Estimation Comments	Non-inferiority of LKM with respect to CPT-C was analyzed as the change rate from baseline to 6-month follow-up between groups (CPT-C minus LKM), with a positive value indicating a greater reduction in scores from baseline for LKM compared to CPT-C.

Adverse Events

Time Frame	From baseline to 6-month follow-up (approximately 9 months total).
Adverse Event Reporting Description	We prospectively monitored hospitalizations, suicidality and death. In addition we recorded events according to the following criteria: An increase of 20 or more points on the total CAPS-5 score since the last assessment point or an increase in depression severity of 2 or more severity categories using a rubric that transformed PROMIS depression values scores to Patient Health Questionnaire (PHQ)-9 scores and categories
Arm/Group Title	Loving-Kindness Meditation		Cognitive Processing Therapy - Cognitive Only
Arm/Group Description	A 12-week duration, 90-minute per session Loving-Kindness Meditation (LKM) course, taught in groups of 10 participants.		A 12-week duration, 90-minute per session Cognitive Processing Therapy (CPT) course, taught in groups of 10 participants.
All Cause Mortality
	Loving-Kindness Meditation		Cognitive Processing Therapy - Cognitive Only
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/91 (2.2%)		0/93 (0%)
Serious Adverse Events
	Loving-Kindness Meditation		Cognitive Processing Therapy - Cognitive Only
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/91 (5.5%)		3/93 (3.2%)
Nervous system disorders
Seizure	0/91 (0%)	0	1/93 (1.1%)	1
Psychiatric disorders
Suicide attempt	0/91 (0%)	0	1/93 (1.1%)	1
Inpatient psychiatric admission	1/91 (1.1%)	1	0/93 (0%)	0
Risk of Harm to Others	0/91 (0%)	0	1/93 (1.1%)	1
Suicidality with Intent or Plan requiring staff intervention	4/91 (4.4%)	4	0/93 (0%)	0
Other (Not Including Serious) Adverse Events
	Loving-Kindness Meditation		Cognitive Processing Therapy - Cognitive Only
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/91 (12.1%)		18/93 (19.4%)
Psychiatric disorders
Increase in depression score	7/91 (7.7%)	91	14/93 (15.1%)	93
Increase in PTSD severity score	4/91 (4.4%)	91	3/93 (3.2%)	93
Risk of harm to others	0/91 (0%)	0	1/93 (1.1%)	93

Limitations/Caveats

The study involved predominantly male veterans from one facility; the results may not generalize to nonveterans or veterans in other regions. Treatment credibility and adequacy of blinding of the clinician-assessor of PTSD symptoms were not assessed.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.