Clinical trial NCT05064813: MBSR Mechanisms in GAD
Official title: Elucidating Neural Mechanisms and Sex Differences in Response to Mindfulness Based Stress Reduction in Generalized Anxiety Disorder
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Generalized Anxiety Disorder
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
First posted: 2021-10-01
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to understand the neural mechanisms that drive response to MBSR compared to stress education in patients with generalized anxiety disorder (GAD), and to examine the degree to which sex differences in MBSR response are explained by sex differences in these mechanisms. A total of 150 eligible participants with a primary diagnosis of GAD will be randomized to either an 8-week group MBSR or stress education program. The study will include preliminary screening, experimental visits, including fMRI, group intervention visits, and assessments at baseline, endpoint, and 3-month follow-up.

Detailed description: Mindfulness-Based Stress Reduction (MBSR) has demonstrated efficacy for Generalized Anxiety Disorder (GAD), yet there remains a major knowledge gap about its neural mechanisms.

This study will examine functional activation of brain regions associated with the fear extinction network (ventromedial prefrontal cortex (vmPFC), hippocampus, and amygdala) as a specific probe of the 'instinctual' type of emotion regulation as well as large-scale functional connectivity as a marker of neural plasticity changes. Sex differences in MBSR-induced neural changes and their relationship to sex differences in clinical GAD response will be examined. Finally, a novel statistical approach will be used to explore whether baseline neural measures can predict neural changes and clinical symptom reduction to identify likely MBSR responders.

The unique combination of a focus on GAD, an anxiety condition with established emotion regulation difficulties implicating target neural circuits, previously demonstrated MBSR efficacy, and sex differences with rigorous fMRI behavioral probes with novel analytic approaches ought to provide major new insights about MBSR versus stress education mechanisms and sex considerations, moving towards precision medicine that could guide future treatment development research.

Eligible participants with Generalized Anxiety Disorder will be 2:1 randomized to group intervention with MBSR or stress education classes. They will participate for 13-14 weeks plus one 3 month follow up assessment (23-24 weeks from screening). Full participation includes screening, baseline, endpoint and 3 month follow up assessments, two sets of experimental days 12 weeks apart which include fMRI scans, and 8 weeks of the assigned group intervention (either MBSR or stress education).

Eligibility criteria: Inclusion Criteria:

* Male or pre-menopausal female outpatients aged 18 to 50 years of age
* A primary mental health complaint (designated by the patient as the most important source of current distress and confirmed on structured clinical interview for DSM-5 diagnoses by a certified clinical evaluator) of Generalized Anxiety Disorder (GAD), as defined by DSM-5 criteria.
* Overall clinical anxiety severity of at least mild as defined by a CGI-S of at least 3.
* Willingness and ability to participate in the informed consent process and comply with the requirements of the study protocol.
* Able to provide proof of COVID-19 vaccination at in person screen visit

Exclusion Criteria:

* A lifetime history of bipolar disorder, schizophrenia, psychosis, or delusional disorders; obsessive-compulsive disorder or an eating disorder in the past 12 months; neurocognitive disorders, intellectual disabilities, communication disorders or other cognitive dysfunction that could interfere with capacity to engage in therapy or complete study procedures; substance or alcohol use disorder (other than nicotine) in the last 6 months or otherwise unable to commit to refraining from alcohol use during the acute period of study participation.
* Patients with significant suicidal ideation (assessed by CSSR-S SI score greater than 2) or who have enacted suicidal behaviors within 6 months prior to intake will be excluded from study participation and referred for appropriate clinical intervention.
* Patients must be free of concurrent benzodiazepine, antipsychotic, and stimulant medication for at least 4 weeks prior to initiation of randomized treatment. Other psychiatric medications such as antidepressants that have been stable for at least 4 weeks prior to randomization will be permitted.
* Inability to understand study procedures or informed consent process, or significant personality dysfunction likely to interfere with study participation (assessed during the clinical interview) or inability to comply with study procedures (such as planned extended travel) assessed on clinical interview
* Serious current unstable medical illness, or a condition for which hospitalization may be likely within the next year as assessed by medical history and physical exam. If any questions about medical safety emerge, consent will be formally obtained to contact patient's PCP in order to determine whether any medical concerns making participation unsafe or not feasible (such as need for extended inpatient care) are present; MBSR and SE, however, do not require intensive exercise capacity or mobility.
* Pregnant women (to be ruled out by urine ß-HCG) and women of childbearing potential who are not using medically accepted forms of contraception (such as IUD, oral contraceptives, barrier devices, condoms and foam, or implanted progesterone rods stabilized for at least 3 months).
* Any concurrent psychotherapy initiated within 3 months of baseline, or ongoing psychotherapy of any duration directed specifically toward treatment of GAD or with any mindfulness and/or meditation component is excluded. Prohibited psychotherapy includes CBT, DBT, ACT, mindfulness based approaches, or psychodynamic therapy focusing on exploring specific, dynamic causes of the GAD symptomatology and providing management skills. General supportive therapy initiated greater than 3 months prior is acceptable.
* Individuals who have completed a course of MBSR or an equivalent meditation training or who have an ongoing regular meditation practice in the past 2 years.
* Patients with a history of head trauma causing loss of consciousness, seizure or ongoing cognitive impairment.
* Contraindications for MRI including metal implants, surgical clips, probability of metal fragments, or braces that are prohibited due to severe risk of injury.
* Left handed

Primary outcomes:
measure: Pre-post changes in fMRI measures of functional activation in the fear extinction network during fear extinction learning
timeFrame: Experimental Days 1 & 2 (Visit 2 & 3) and Experimental Days 3 & 4 (Visit 9 & 10)
measure: Pre-post changes in fMRI measures of functional activation in the whole brain neural connectivity during fear extinction learning
timeFrame: Experimental Days 1 & 2 (Visit 2 & 3) and Experimental Days 3 & 4 (Visit 9 & 10)
Secondary outcomes:
measure: Change in Skin Conductance Response (SCR).
timeFrame: Experimental Days 1 & 2 (Visit 2 & 3) and Experimental Days 3 & 4 (Visit 9 & 10)
Other outcomes:
Locations:
city: New York
country: United States
facility: NYU Langone Health
state: New York
Study officials:
affiliation: NYU Langone Health
name: Naomi Simon, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: NYU Langone Health
name: Candace Raio, PhD
role: PRINCIPAL_INVESTIGATOR
References: