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

Post Traumatic Stress Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03489122
• Other study ID #: MHBB-001-17S
• Status: Terminated
• Phase: N/A
• Start date: January 11, 2022
• Est. completion date: June 15, 2022

Study information

• Verified date: March 2023
• Source: VA Office of Research and Development
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: June 15, 2022
• Est. primary completion date: June 15, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Disease
• Post Traumatic Stress Disorder
• Stress Disorders, Post-Traumatic
• Stress Disorders, Traumatic

Intervention

Behavioral:
• yoga
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.
• walking
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.

Locations

Country	Name	City	State
United States	VA Bedford HealthCare System, Bedford, MA	Bedford	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
VA Office of Research and Development

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Respiratory Sinus Arrhythmia (RSA)	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.	Before Scans 1-3, before and after the week 4, 8, and 12 evaluations
Other	Clinician Administered Posttraumatic Stress Scale (CAPS)	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.	Screening and week 12 evaluation
Other	State Trait Anxiety Inventory-State (STAI)	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.	Before Scans 1-3, before and pre and post the week 4, 8, and 12 evaluations
Other	Exercise Induced Feeling Inventory (EIF)	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.	Before Scans 1-3, before and pre and post the week 4, 8, and 12 evaluations
Other	Pittsburgh Sleep Quality Inventory	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.	Obtained at screening, and weeks 4, 8, and 12 evaluations.
Other	Beck Depression Inventory II (BDI-II)	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.	Screening, Scan 1, Scan 2, weeks 4, 8, 12 evaluations and follow-up at 2 and 6 months.
Other	Post Traumatic Check List - Civilian (PCL)	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	Screening, Scan 1, Scan 2, and weeks 4, 8, 12 evaluations
Other	Brief Pain Inventory (BPI)	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.	Screening, Scan 1, Scan 2, and weeks 4, 8, 12 evaluations.
Primary	Hamilton Depression Rating Scales Change	The Hamilton Depression Rating Scale for Depression is a clinician administered scale used to assess depressive symptoms	Screening, Scan 1, Scan 2, at week 4, 8, 12 and follow-up at 2 and 6 months
Secondary	Gamma Amino Butyric Acid (GABA) Change	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.	12 weeks, up to 22 weeks