A Randomized Control Trial Treating Depression With Yoga and Coherent Breathing Versus Walking in Veterans

A Randomized Control Trial Treating Depression With Yoga and Coherent Breathing Versus Walking in Veterans

A Randomized Control Trial Treating Depression With Yoga and Coherent Breathing Versus Walking in Veterans

Enrollment was far from meeting target expectations, and the PO did not believe the study could achieve numbers before the end of the award

The proposed study addresses a gap regarding the need for effective Major Depressive Disorder (MDD) treatments and the 40% of individuals treated with antidepressant medications that do not achieve full remission. This study tests a novel approach for treating MDD in a Randomized Control Trial (RTC) using yoga versus walking interventions to correct an imbalance in the Autonomic Nervous System; an over active Sympathetic Nervous System (fight or flight) an underactive Parasympathetic Nervous System (PNS) (rest, renewal and social engagement) and associated under activity in the neurotransmitter, gamma aminobutyric acid (GABA). This novel approach is complimentary to the use of antidepressant medications that primarily target the monoamine systems. Low activity in the PNS and GABA systems are also found in MDD, PTSD, and Alcohol Use Disorder, disorders representing a high healthcare burden in the Veteran population. This intervention has potential to provide relief for MDD and other disorders relevant the Veteran population

Suspension of all non-essential research due to COVID Overview The study tests the hypothesis that an imbalance in the autonomic nervous system with to much sympathetic tone (Fight or Flight) and to little parasympathetic tone (rest, renewal and social engagement) and associated low activity in the neurotransmitter gamma aminobutyric acid (GABA) is associated with negative emotional states and may be a crucial underlying link between negative emotions and poor health such that the correction of these imbalances will be associated with decreased depressive symptoms in Veterans with Major Depressive Disorder (MDD). Study Design: This is a Phase 2, longitudinal, efficacy, randomized controlled trial. Veterans with MDD will be evaluated for eligibility and randomized to 12-week intervention providing two-sessions per week of either an intervention of yoga and coherent breathing at five breaths per minute or walking at 2.5 miles an hour, such that the groups are matched for metabolic demand, interaction with research staff and group effect. Depression scales will be collected at baseline and weeks 4, 8, and 12. Mood scales and RSA will be collected at baseline and pre and post interventions at weeks 4, 8, and 12. Magnetic resonance spectroscopy (MRS) data for thalamic GABA levels will be collected at baseline (Scan 1), after the 12-week intervention (Scan 2) which is immediately followed by the assigned intervention and Scan 3. The primary outcome measure is depression symptoms assessed using established rating scales. The secondary outcome measure is the thalamic GABA levels. The tertiary outcome measure is Respiratory Sinus Arrhythmia (RSA), a measure of high frequency Heart Rate Variability and a marker of parasympathetic tone. Evaluations are designed to address changes over the course of the study, and acute changes before and after interventions at week 4, 8, and 12 evaluations. Instruments: Depression scales include the Hamilton Rating Scale for Depression-17 (HDRS) and the Beck Depression Inventory II (BDI-II). Mood scales include the Spielberger State -Trait Anxiety Inventory (STAI) and the Exercise -Induced Feeling Inventory (EIFI). Post Traumatic Stress Disorder (PTSD) scales include the Clinician Administered Posttraumatic Stress Scale (CAPS) and the PTSD Check List - Civilian (PCL-C). Inclusion Criteria: The study will include 18 to 65 year old males and females Veterans with a current diagnosis of MDD who have a HDRS scores to 14 at screening. If subjects have been taking a stable dose of antidepressants that target a monoamine system for at least three months with no anticipated changes during the study, they will be allowed to continue their medication. Exclusion Criteria: The following are not allowed: history of psychosis or bipolar illness; history of suicidal ideation with intent in the last year; current mind-body practice (e.g., yoga, Tai Chi, Qigong, breathing practices, or meditation); more than three current criteria for Alcohol or Substance Use Disorder using DSM-V criteria; a current Substance Use Disorder, a neurologic or medical condition that could compromise subject safety or the integrity of the study. Blinding: Individuals scoring the depression scales, or analyzing the MRS and RSA data will be blind to group assignment. Hypothesis: I.a: The yoga group but not the walking group will show decreased in depressive symptoms on the HDRS and BDI-II from screening to week 12. 1.b: Subjects who are still depressed at baseline despite treatment with a stable dose (> 3 months) of antidepressants treatment will show decreased depressive symptoms in the yoga but not the walking group. 1.c: If present at baseline, there will be a greater decrease in PTSD symptoms on the CAPS in the yoga compared to the walking group. 2: There will be an increase in GABA levels over the course of the three scans in the yoga but not the walking group. 3: Over the course of the intervention and from pre to post-intervention at weeks 4, 8, and 12 there will be an improvement in the mood scales (STAI and EIFI), and increase in RSA in the yoga but not the walking group.

Depressive Disorder, Major, yoga, breathing exercise, parasympathetic, anxiety, Post Traumatic Stress Disorder, polyvagal

Participants will be randomized to a Iyengar yoga and coherent breathing or walking intervention. Two interventions a week for 12 weeks are prescribed

This is a behavioral intervention such that participants cannot be blinded. Participant questionnaires are fill out by participants without staff involvement. Outcome assessors: Clinicians completing the depression scales will be blinded to group assignment. Individuals analyzing magnetic resonance spectroscopy (MRS) and electrocardiogram (ECG) data will receive blinded data for analysis

The yoga intervention consists of Iyengar yoga method and coherent breathing sessions for 90 minutes twice a week or a maximum of 24 interventions over the 12 week intervention.

The walking intervention consists of walking sessions at 2.5 miles an hour on a flat surface for 60 minutes twice a week or a maximum of 24 interventions over the 12 week intervention.

The yoga intervention consists of Iyengar yoga method and coherent breathing sessions for 90 minutes twice a week or a maximum of 24 interventions over the 12 week intervention.

The walking intervention consists of walking sessions at 2.5 miles an hour on a flat surface for 60 minutes twice a week or a maximum of 24 interventions over the 12 week intervention.

The Hamilton Depression Rating Scale for Depression is a clinician administered scale used to assess depressive symptoms

Magnetic Resonance Spectroscopy (MRS) will be used to measure GAB levels in the left thalamus Scan 1 prior to randomization, Scan 2 after the 12-week intervention, immediately after Scan 2 there will be a yoga or walking intervention determined by group assignment that will be immediately followed by Scan 3. Participation in the study maybe up to 22 weeks due to the need to scan females who are cycling in the first half of their menstrual cycle.

Electrocardiogram data will be obtained at rest, during a 3 minute aerobic step test and during recovery for RSA analysis at the above times. RSA measures the vagal component of heart rate variability. It is a marker of parasympathetic activity.

This is an exploratory measure. Clinician Administered Posttraumatic Stress Scale (CAPS) is a clinician administered interview to diagnose the severity of Post Traumatic Stress Disorder (PTSD). Decreasing CAPS scores are a marker of decreasing PTSD symptoms. CAPS scores of greater than or equal to 20 indicate at least mild PTSD.

The State-Trait Anxiety Inventory (STAI) is a self-administered instrument designed for serial assessment of state anxiety with higher scores indicating higher anxiety. Corrections for multiple comparisons will be made for non-exploratory Other Pre-specified outcome measures.

Exercise-Induced Feeling Inventory (EIFI) is a self-administered instrument designed to assess four distinct feeling states associated with bouts of physical activity: Revitalization, Tranquility, Positive Engagement, and Physical Exhaustion. Improvements are associated with increased scores on Revitalization, Tranquility, Positive Engagement, and decreased scores on Physical Exhaustion. Corrections for multiple comparisons will be made for non-exploratory Other Pre-specified outcome measures.

Pittsburgh Sleep Quality Index (PSQI) is a self-administered instrument that assesses 9 factors of sleep over a month period, providing a composite score, with higher scores indicating poorer sleep quality. Corrections for multiple comparisons will be made for non-exploratory Other Pre-specified outcome measures.

Beck Depression Inventory (BDI-II) is a 21-item self-administered instrument designed for the assessment of depressive symptoms, with higher scores reflecting greater severity. A score of greater than or equal to 14 indicates Major Depressive Disorder. The BDI-II is a self-administered depression scale. Corrections for multiple comparisons will be made for non-exploratory Other Pre-specified outcome measures.

PTSD Check List - Civilian (PCL-C) is a 17-item self-administered scale corresponding to Diagnostic and Statistical Manual of Mental Disorders (DSM) IV criteria for PTSD. Because not all Veterans have combat experience and not all trauma is from a military experience, the civilian version of the PCL will be used. Corrections for multiple comparisons will be made for non-exploratory Other Pre-specified outcome measures

Brief Pain Inventory (BPI), an eleven point Likert Scale of pain intensity will be used to assess pain over the last 24 hours. Corrections for multiple comparisons will be made for non-exploratory Other Pre-specified outcome measures.

Inclusion Criteria: Fluent in English Understands the risks and benefits of the study as listed in the Post Consent Quiz Females must agree to use an acceptable form of birth control [Human Subjects] Females are not pregnant and do not intend to become pregnant during the study Meets criteria for MDD on the MINI Hamilton Rating Scale for Depression (HDRS) scores to 14 at screening If subjects have been taking antidepressants that target a monoamine system, the dose has been stable for at least three months with no anticipated changes during the study If subjects have been in a stable form of psychotherapy for three months, with no anticipated changes in their psychotherapy during the study (this would exclude time-limited manual-driven therapies such Cognitive Behavioral Therapy) Reliable contact information provided Has completed all required screening instruments and evaluations Exclusion Criteria: History of psychosis History of bipolar illness History of suicidal ideation with intent and or a suicide attempt in the last year Desire to be treated for MDD with a new treatment during the study such as pharmacotherapy, somatic therapy or psychotherapy Current mind-body practice defined as more than 6 one-hour sessions in the last 6 months yoga Tai Chi Qigong breathing practices, or meditation Participates in physical exercise > 5 hours/week that is equivalent to or greater than 6 metabolic equivalents (METs) in intensity Has been treated psychotropic medications such as mood stabilizers Valproic Acid Carbamazepine Lithium Benzodiazepines or pain medication other than Non Steroidal Anti-Inflammatory Drugs (NSAIDS) in the last three months except for procedure related pain management dental procedures Has more than three current criteria for Alcohol or Substance Use Disorder using DSM-V criteria Has a neurologic or medical condition that in the opinion of the PI could compromise subject safety or the integrity of the study In the opinion of the PI, would not be expected to complete the study, or their participation would be jeopardized subject safety or the integrity of the study Has an Axis-I diagnosis, other than depression except as listed, that in the opinion of the PI would interfere with the subject's participation in this study Anxiety disorders with current symptoms that would impair participation in the study Obsessive Compulsive Disorder (OCD) or agoraphobia that would prevent intervention attendance Post Traumatic Stress Disorder with dissociation or flashbacks that could be triggered by the yoga intervention Claustrophobia that would prevent scanning Traumatic Brain Injury (TBI) with greater than 30 minutes loss of consciousness Must have a period of 48 hours of no alcohol use and 24 hours of no nicotine use on TLFB to participate in scanning given the effects of tobacco smoke and alcohol consumption on the GABA system

Mechanisms for public access to final data sets underlying publications from this research: A limited Dataset (LDS) will be created and shard pursuant to a Data Use Agreement (DUA) appropriately limiting use of the dataset and prohibiting the recipient form identifying or re-identifying (or taking steps to identify or re-identify) any individual whose data are included in the data set.

Final data sets will be available electronically after publication of the hypotheses or 5 years after protocol completion.

Data will be provided to qualified researchers after the written request of their data use plan is approved in writing by the Bedford VA research office. Original research team members are allowed to review potential publications to assure final data set use is consistent with collection circumstances. Member that review potential publications will be included as authors.