Research Protocol for Karuna Labs Inc.: Safety and Efficacy of Virtual Reality Graded Motor Imagery for Chronic Pain
Condition: Chronic Pain; Low Back Pain; Fibromyalgia; Upper Extremity Dysfunction; Complex Regional Pain Syndromes; Phantom Limb Pain; Rheumatoid Arthritis; Carpal Tunnel Syndrome; Repetitive Strain Injury
MeSH terms: Fibromyalgia; Carpal Tunnel Syndrome; Complex Regional Pain Syndromes; Reflex Sympathetic Dystrophy; Phantom Limb; Syndrome; Low Back Pain; Chronic Pain; Cumulative Trauma Disorders
Study type: Observational

Summary: 
      The purpose of this study is to investigate, in two phases: (1) the feasibility and safety of
      Virtual Embodiment Therapy in treating chronic pain of lower back and upper limbs and (2) the
      efficacy of Virtual Embodiment Therapy on chronic pain disorders of the lower back and upper
      limbs. In phase 1, we will investigate the feasibility, safety, and side effects related to
      this treatment by assessing simulator sickness. In phase 2, which in contingent on successful
      completion of phase 1, we will assess symptoms of pain specific to the region treated, fear
      and avoidance behavior, and depression symptoms before and after 8 sessions of treatment with
      Virtual Embodiment Therapy in order to assess efficacy. This study will be single-blinded,
      because the participation of the clinician is necessary to ensure proper administration of
      the therapy, as well as to monitor in the event of adverse reactions.
    

Detailed description: 
      This multi-site study aims to investigate the feasibility, safety, and efficacy of using
      embodied virtual reality graded motor imagery software to treat adults with diagnosed chronic
      central pain conditions in two bodily regions: chronic pain in the lower back and in the
      upper limbs. The research will be conducted in two phases, the second of which is contingent
      upon successful completion of the first. The first phase will involve piloting a novel
      virtual reality treatment for chronic pain to investigate feasibility and safety with a
      smaller number of patients (N=30 for each condition). The second phase of the research will
      investigate efficacy using a single-blinded randomized control study design with sham
      control. Chronic pain conditions of the lower back and upper limbs will be investigated
      separately, and power analyses have been conducted to determine optimal study size, which is
      N=200 for each portion.

      Central pain is defined as pain that originates in the central nervous system, and is not
      immediately due to injury, but is possibly a delayed reaction to injury. Example conditions
      eligible for this study include chronic lower back pain, as well as phantom limb pain,
      complex regional pain syndrome, carpal tunnel syndrome, post-stroke limb pain, and repetitive
      strain injuries of the shoulder, arm or hand. In the pilot phase of the study, 30 subjects
      with chronic lower back pain and 30 subjects with chronic upper limb pain will receive 8
      sessions of graded motor imagery virtual reality therapy. Contingent on the success of the
      pilot, defined as completion of 8 session with no adverse events, and trends indicating
      improvement of range of motion, pain, fear/avoidance, and depression symptoms, the randomized
      control trial phase of the research will proceed. In the randomized phase, subjects will be
      randomized into active or control conditions. Active condition subjects will receive 8
      sessions of graded motor imagery in virtual reality, and control condition subjects will
      receive a non-embodied sham virtual reality experience. This study will investigate the
      safety and feasibility of this approach, as well as its effects on pain symptoms.

      This product is considered a non-significant risk device, as is explained in the accompanying
      letter from the sponsor, Karuna Labs Inc. A request for feedback from the presubmission
      program of the U.S. Food and Drug Administration has additionally been submitted.
    

Intervention name(s): Karuna Labs Virtual Reality Software
Intervention type(s): Device
Intervention description(s): The subjects will engage in the three therapeutic modules: laterality, motor imagery, and 'mirroring.' The decision of which module to employ will be based on the subject's readiness and comfort on a case-by-case basis. A subject visit can be expected to last 40 minutes, with enough time to complete PHQ-9, and to accustom to the virtual reality setup by playing in a non-therapeutic virtual environment should they choose to do so. Time in the virtual reality is expected to last approximately 20 minutes per session.
Observational model: Case-Only
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        People diagnosed with chronic pain disorders of the lower back or upper limbs with a
        continual duration of at least 6 months