Clinical trial NCT03489122: A Randomized Control Trial Treating Depression With Yoga and Coherent Breathing Versus Walking in Veterans
Official title: A Randomized Control Trial Treating Depression With Yoga and Coherent Breathing Versus Walking in Veterans
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Depressive Disorder, Major
Post Traumatic Stress Disorder
Keywords: Depressive Disorder, Major
yoga
breathing exercise
parasympathetic
anxiety
Post Traumatic Stress Disorder
polyvagal
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2018-04-05
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized to a Iyengar yoga and coherent breathing or walking intervention. Two interventions a week for 12 weeks are prescribed
Primary purpose: TREATMENT

Brief 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

Detailed description: Suspension of all non-essential research due to Corona Virus Disease (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 the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (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.

Eligibility criteria: 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-International Neuropsychiatric Interview (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 the Timeline Followback (TLFB) to participate in scanning given the effects of tobacco smoke and alcohol consumption on the GABA system

Primary outcomes:
measure: Hamilton Depression Rating Scales Change
timeFrame: Screening, week 4, week 8, week 12
Secondary outcomes:
measure: Gamma Amino Butyric Acid (GABA) Change
timeFrame: 12 weeks, up to 22 weeks
Other outcomes:
measure: Respiratory Sinus Arrhythmia (RSA)
timeFrame: Before Scans 1-3, before and after the week 4, 8, and 12 evaluations
measure: Clinician Administered Posttraumatic Stress Scale (CAPS)
timeFrame: Screening and week 12 evaluation
measure: State Trait Anxiety Inventory-State (STAI)
timeFrame: Screening, and pre and post the week 4, 8, and 12 evaluations
measure: Exercise Induced Feeling Inventory (EIFI)
timeFrame: Screening, and pre and post the week 4, 8, and 12 evaluations
measure: Pittsburgh Sleep Quality Inventory
timeFrame: Obtained at screening, and weeks 4, 8, and 12 evaluations.
measure: Beck Depression Inventory II (BDI-II)
timeFrame: Screening, weeks 4, 8, 12 evaluations
measure: Post Traumatic Check List - Civilian (PCL)
timeFrame: Screening, and weeks 4, 8, 12 evaluations
measure: Brief Pain Inventory (BPI)
timeFrame: Weeks 4, 8, 12 evaluations.
Locations:
city: Bedford
country: United States
facility: VA Bedford HealthCare System, Bedford, MA
state: Massachusetts
Study officials:
affiliation: VA Bedford HealthCare System, Bedford, MA
name: Chris C Streeter, MD
role: PRINCIPAL_INVESTIGATOR
References: