MindREaL: Mindfulness for Resilience in Early Life

• Sponsor: Laureate Institute for Brain Research, Inc. (Other)
• Overall Status: Completed
• CT.gov ID: NCT03633903
• Collaborator: Oklahoma State University (Other)
• Enrollment: 40
• Location: 1
• Arms: 2
• Actual Duration (Months): 7.8
• Patients Per Site Per Month: 5.1

Study Details

Study Description

Brief Summary

Early life stress (ELS) is associated with a number of psychiatric and medical conditions later in life, thought to be caused by subsequent disruptions in biological processes involved in regulation of stress responses. Given that these alterations have long-lasting effects, there is a great need for effective preventative interventions. The long-term goal of this project is to identify early interventions that may most powerfully mitigate risk for psychiatric illness among adolescents with exposure to early life stress (ELS), with a focus on interventions that can be widely and effectively implemented, have the potential for long-lasting benefits, and can effectively engage targeted neurobiological processes and networks. The specific aims of the present study are to 1) examine how ELS impacts biological processes associated with regulation of stress, and 2) identify how MBI impacts affective symptoms and biological processes dysregulated by ELS.

This study supports the efforts to reduce the effects of early adversity in children by testing an impact of an effective psychological intervention on disrupted biological processes caused by early adversity. Successful achievement of the proposed aims will contribute to a) the knowledge base needed to reduce the effects of trauma and stress in children and families and b) the development of easily implemented and disseminated preventative interventions.

The proposed study will utilize a multi-method design to examine the effect of mindfulness on biological processes (i.e., stress responses) disrupted by exposure to ELS among adolescents age 13 to 15. Adolescents will first complete self-report measures of childhood adverse experiences, trauma, and neglect. Forty eligible adolescents will be next randomly assigned to either an eight session mindfulness-based stress reduction intervention for teens or no treatment. Pre- and post-intervention assessment will include (a) self-report measures of symptoms and emotion regulation, (b) a blood draw for assessment of inflammatory markers and gene expression, and (c) a stress task with saliva cortisol collected before and after this task.

Condition or Disease	Intervention/Treatment	Phase
Adolescent With Early Life Stress; Resilience	Behavioral: Mindfulness	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Adolescents are randomly assigned to either a mindfulness intervention or no intervention.Adolescents are randomly assigned to either a mindfulness intervention or no intervention.
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Mindfulness for Resilience in Early Life
• Actual Study Start Date: Jul 12, 2018
• Actual Primary Completion Date: Mar 7, 2019
• Actual Study Completion Date: Mar 7, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Mindfulness Mindfulness: Eight sessions, twice per week over four weeks. Surveys administered prior to each session.	Behavioral: Mindfulness; Mindfulness based stress reduction adapted for teens is a mindfulness intervention designed to aid adolescents in understanding stress, better coping with stress, and promoting resilience
No Intervention: Control Treatment as usual (i.e., pharmacotherapy, psychotherapy, etc.) for the four week duration with twice weekly surveys administered.

Outcome Measures

Primary Outcome Measures

1. Cortisol Reactivity [Baseline (pre-intervention); Follow-up (post-intervention) at 6-8 weeks from baseline]

   Change in level of cortisol in saliva following a social stress test. Subjects completed the Trier Social Stress Test for Children (TSST-C) at baseline and follow-up. The TSST-C consists of public speaking and serial subtraction components in front of two research confederates. The test takes approximately 20 minutes to complete. Salivary cortisol was collected 20 minutes prior to TSST-C, and 20 minutes following the end of the TSST-C, such that the TSST-C task with data collection spanned approximately one hour.

2. Immune System Activity [Baseline (pre-intervention); Follow-up (post-intervention) at 6-8 weeks from baseline]

   Change in level of interleukin 6 (IL-6) and C-reactive protein (CRP) in blood

Secondary Outcome Measures

1. Mood and Feelings Questionnaire [Baseline (pre-intervention); Follow-up (post-intervention) at 6-8 weeks from baseline]

   Measure Description: We used the Mood and Feelings Questionnaire - Short Form (MFQ-sf) to characterize symptoms of anxiety and depression. The MFQ-sf is a 13-item questionnaire with a simple sum score for the entire scale. Minimum score = 0, maximum score = 26. Scores of 8 or more indicate moderate depression. Codings reflect whether the phrase was descriptive of the subject most of the time, sometimes, or not at all. Higher scores indicate greater symptoms of anxiety/depression, while lower scores indicate less anxiety/depression.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 13 Years to 15 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Age 13.00 to 15.99 years at time of baseline assessment

• Able to validly and safely complete baseline assessments

• All genders

• All races

• Eligibility as a subject with early life stress will be determined by:

• Scoring 4 or greater on Adverse Childhood Experiences (ACE) scale, with at least two experiences having occurred prior to age 10.

Exclusion Criteria:

• No biological parent or legal guardian identified to give permission for minor to participate

• History of neurological disorders including seizure disorder, cerebral palsy, or other conditions requiring neurological or medical care, being managed for migraines (e.g., daily prophylactic medication, seeing a neurologist for migraines), or a diagnosis of Developmental Delay, including severe learning disorder, mental retardation, pervasive developmental disorder, or other conditions requiring repeated and persistent specialized education.

• Current psychotic disorder, bipolar disorder, obsessive-compulsive and related disorders, substance use disorder, or conduct disorder.

• Current active suicidal ideation.

• Current use of medications with major effects on brain function or blood flow (e.g., antipsychotics, mood stabilizers); ADHD medications and SSRIs, that have been stable for at least 6 weeks, are not exclusionary since their use is associated with conditions that confer risk for monitored disorders that emerge in adolescence, and assessment of these individuals will provide useful data to the scientific community. Youth on ADHD medications and SSRIs will not be asked to go off their medications.

• Not fluent in English

• Non-correctable vision, hearing or sensorimotor impairments, as protocol elements may not be valid.

• Youth planning to move to an area not within reasonable traveling distance of LIBR; knowledge at baseline that treatment completion / follow-up will not be possible.

• Youth appears to be high/intoxicated, or withdrawing from the effects of alcohol or drugs at time of enrollment.

• Youth / parent who are unable or unwilling to provide biological samples (i.e., blood draws or saliva collection).

• Female youth who are pregnant

• Youth who are currently in unsafe environments (e.g., currently living with an abusive parent)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Laureate Institute for Brain Research	Tulsa	Oklahoma	United States	74136

Sponsors and Collaborators

• Laureate Institute for Brain Research, Inc.
• Oklahoma State University

Investigators

• Principal Investigator: Namik Kirlic, PhD, Laureate Institute for Brain Research

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 31, 2018

More Information

Publications

None provided.

• Responsible Party: Laureate Institute for Brain Research, Inc.
• ClinicalTrials.gov Identifier: NCT03633903
• Other Study ID Numbers: LIBR # 2018-003-00
• First Posted: Aug 16, 2018
• Last Update Posted: Aug 19, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Laureate Institute for Brain Research, Inc.: Early life stress; Adolescent; Mindfulness; Neurobiological; Stress; Resilience
• Additional relevant MeSH terms: Stress, Psychological

Study Results

Participant Flow

Recruitment Details	Adolescents and their families were recruited from the community using flyers, radio advertisements, billboards, and a school-based messaging platform (e.g., PeachJar).

Arm/Group Title	Mindfulness	Control
Arm/Group Description	Mindfulness: Eight sessions, twice per week over four weeks Mindfulness: Mindfulness based stress reduction adapted for teens is a mindfulness intervention designed to aid adolescents in understanding stress, better coping with stress, and promoting resilience	Treatment as usual, inactive control group
Period Title: Overall Study
STARTED	22	18
Intent to Treat	0	18
COMPLETED	16	11
NOT COMPLETED	6	7

Baseline Characteristics

Arm/Group Title	Mindfulness	Control	Total
Arm/Group Description	Mindfulness: Eight sessions, twice per week over four weeks Mindfulness: Mindfulness based stress reduction adapted for teens is a mindfulness intervention designed to aid adolescents in understanding stress, better coping with stress, and promoting resilience	Treatment as usual, inactive control group	Total of all reporting groups
Overall Participants	22	18	40
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	14.33 (0.73)	14.29 (0.77)	14.31 (0.75)
Sex: Female, Male (Count of Participants)
Female	7 31.8%	8 44.4%	15 37.5%
Male	14 63.6%	9 50%	23 57.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 9.1%	1 5.6%	3 7.5%
Not Hispanic or Latino	19 86.4%	16 88.9%	35 87.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 9.1%	2 11.1%	4 10%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	4 18.2%	5 27.8%	9 22.5%
White	10 45.5%	9 50%	19 47.5%
More than one race	5 22.7%	0 0%	5 12.5%
Unknown or Not Reported	0 0%	1 5.6%	1 2.5%
Change in salivary cortisol (μg/dL) [Mean (Standard Deviation) ]
baseline, pre stress induction	0.12 (0.89)	-0.16 (1.15)	-0.02 (1.02)
baseline, post stress induction	-0.22 (0.88)	0.27 (1.10)	0.025 (0.99)
C-reactive protein (mg/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/L]	1.16 (3.82)	2.39 (5.75)	1.775 (4.785)
Interleukin-6 (pg/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [pg/mL]	0.47 (0.48)	0.83 (1.19)	0.65 (0.835)
Depression and Anxiety Symptoms (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	6.81 (4.53)	9.39 (6.54)	8.1 (5.53)

Outcome Measures

1. Primary Outcome

Title	Cortisol Reactivity
Description	Change in level of cortisol in saliva following a social stress test. Subjects completed the Trier Social Stress Test for Children (TSST-C) at baseline and follow-up. The TSST-C consists of public speaking and serial subtraction components in front of two research confederates. The test takes approximately 20 minutes to complete. Salivary cortisol was collected 20 minutes prior to TSST-C, and 20 minutes following the end of the TSST-C, such that the TSST-C task with data collection spanned approximately one hour.
Time Frame	Baseline (pre-intervention); Follow-up (post-intervention) at 6-8 weeks from baseline

Outcome Measure Data

Analysis Population Description

Two subjects were removed from all analyses due to not having usable baseline data and withdrawing prior to intervention. One was removed from each group, such than N=22-1=21 analyzed for mindfulness and N=18-1=17 for control.

Arm/Group Title	Mindfulness	Control
Arm/Group Description	Mindfulness: Eight sessions, twice per week over four weeks Mindfulness: Mindfulness based stress reduction adapted for teens is a mindfulness intervention designed to aid adolescents in understanding stress, better coping with stress, and promoting resilience	Treatment as usual, inactive control group
Measure Participants	21	17
follow-up, pre stress induction	-0.21 (1.05)	0.34 (0.85)
follow-up, post stress induction	0.05 (1.16)	-0.08 (0.76)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mindfulness, Control
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.05
	Comments	The reported p-value was calculated and is not indicating a threshold for significance. This applies to the change from row 1 to row 3 (e.g., baseline pre TSST-C versus follow-up timepoint pre TSST-C)
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.04
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mindfulness, Control
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.05
	Comments	The reported p-value was calculated and is not indicating a threshold for significance. This is for the difference from row 1 to row 2 (baseline pre versus baseline post TSST-C)
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.77
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Mindfulness, Control
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.40
	Comments	The reported p-value was calculated and is not indicating a threshold for significance. Comparing row 1 and row 4 (baseline pre TSST-C versus follow-up post TSST-C).
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.38
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Immune System Activity
Description	Change in level of interleukin 6 (IL-6) and C-reactive protein (CRP) in blood
Time Frame	Baseline (pre-intervention); Follow-up (post-intervention) at 6-8 weeks from baseline

Outcome Measure Data

Analysis Population Description

Two subjects were removed from all analyses due to not having usable baseline data and withdrawing prior to intervention. One was removed from each group, such than N=22-1=21 analyzed for mindfulness and N=18-1=17 for control.

Arm/Group Title	Mindfulness	Control
Arm/Group Description	Mindfulness: Eight sessions, twice per week over four weeks Mindfulness: Mindfulness based stress reduction adapted for teens is a mindfulness intervention designed to aid adolescents in understanding stress, better coping with stress, and promoting resilience	Treatment as usual, inactive control group
Measure Participants	21	17
CRP (followup)	0.83 (1.45)	0.99 (1.32)
I'll-6 (followup)	0.46 (0.32)	0.66 (0.65)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mindfulness, Control
	Comments	Comparing group differences (CRP biomarker) in mindfulness versus control at baseline versus follow-up timepoints.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.39
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.35
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mindfulness, Control
	Comments	Comparing group differences (IL-6 biomarker) in mindfulness versus control at baseline versus follow-up timepoints.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.95
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Mood and Feelings Questionnaire
Description	Measure Description: We used the Mood and Feelings Questionnaire - Short Form (MFQ-sf) to characterize symptoms of anxiety and depression. The MFQ-sf is a 13-item questionnaire with a simple sum score for the entire scale. Minimum score = 0, maximum score = 26. Scores of 8 or more indicate moderate depression. Codings reflect whether the phrase was descriptive of the subject most of the time, sometimes, or not at all. Higher scores indicate greater symptoms of anxiety/depression, while lower scores indicate less anxiety/depression.
Time Frame	Baseline (pre-intervention); Follow-up (post-intervention) at 6-8 weeks from baseline

Outcome Measure Data

Analysis Population Description

Two subjects were removed from all analyses due to not having usable baseline data and withdrawing prior to intervention. One was removed from each group, such than N=22-1=21 analyzed for mindfulness and N=18-1=17 for control.

Arm/Group Title	Mindfulness	Control
Arm/Group Description	Mindfulness: Eight sessions, twice per week over four weeks Mindfulness: Mindfulness based stress reduction adapted for teens is a mindfulness intervention designed to aid adolescents in understanding stress, better coping with stress, and promoting resilience	Treatment as usual, inactive control group
Measure Participants	21	17
Mean (Standard Deviation) [units on a scale]	3.82 (4.61)	8.17 (8.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mindfulness, Control
	Comments	Comparing group differences (symptoms of anxiety/depression) in mindfulness versus control at baseline versus follow-up timepoints.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.08
	Comments	the calculated p value.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.13
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Adverse events were monitored throughout baseline (T1), 8 sessions of twice-weekly intervention where survey responses were recorded and the MBSR-T group had group intervention (T2-T9), and follow-up (T10).
Adverse Event Reporting Description	No adverse events were reported or observed.
Arm/Group Title	Mindfulness		Control
Arm/Group Description	Mindfulness: Eight sessions, twice per week over four weeks Mindfulness: Mindfulness based stress reduction adapted for teens is a mindfulness intervention designed to aid adolescents in understanding stress, better coping with stress, and promoting resilience		Treatment as usual, inactive control group
All Cause Mortality
	Mindfulness		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/18 (0%)
Serious Adverse Events
	Mindfulness		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/18 (0%)
Other (Not Including Serious) Adverse Events
	Mindfulness		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/18 (0%)

Limitations/Caveats

[Not Specified]

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.