Pain Exposure Physical Therapy (PEPT) Versus CBO in Patients With Complex Regional Pain Syndrome Type I (CRPS-1)
Condition: Complex Regional Pain Syndrome, Type I
MeSH terms: Complex Regional Pain Syndromes; Reflex Sympathetic Dystrophy; Syndrome; Somatoform Disorders
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      The current Dutch CBO guideline treatment of Complex Regional Pain Syndrome Type I (CRPS-1)
      is very disappointing with chronification, disability and subsequent high medical costs and
      personal suffering. A possible better treatment is intensive function-oriented physical
      therapy or Pain Exposure in Physical Therapy (PEPT). However, there are no adequate studies
      performed that demonstrate the efficacy of PEPT and therefore PEPT is lacking in the Dutch
      CBO CRPS-1 guidelines. Despite a lacking scientific argumentation, the PEPT approach or
      Macedonian therapy, is now being adopted on a large scale among physical therapists in The
      Netherlands. There are two level C retrospective cohort studies demonstrating a promising and
      clinical relevant beneficial effect on pain and function after PEPT. In response to the
      growing demand for scientific argumentation among doctors and physical therapists with
      respect to the efficacy of PEPT, we conducted a pilot study at the UMC St Radboud Nijmegen.
      The results of this pilot study were very promising and therefore, we decided to design a
      large RCT to investigate the treatment effects and costs in CRPS patients treated with PEPT
      compared to CRPS patients treated with usual therapy according to the Dutch CBO guidelines.
    

Detailed description: 
      Hypothesis:

      PEPT is expected to be 30% more effective and around three-folds cheaper than usual therapy
      (CBO)

      Objective:

      The current Dutch CBO guideline treatment of Complex Regional Pain Syndrome Type I (CRPS-1)
      is very disappointing with chronification, disability and subsequent high medical costs and
      personal suffering. A possible better treatment is intensive function-oriented physical
      therapy or Pain Exposure in Physical Therapy (PEPT). However, there are no adequate studies
      performed that demonstrate the efficacy of PEPT and therefore PEPT is lacking in the Dutch
      CBO CRPS-1 guidelines. Despite a lacking scientific argumentation, the PEPT approach or
      Macedonian therapy, is now being adopted on a large scale among physical therapists in The
      Netherlands. There are two level C retrospective cohort studies demonstrating a promising and
      clinical relevant beneficial effect on pain and function after PEPT. In response to the
      growing demand for scientific argumentation among doctors and physical therapists with
      respect to the efficacy of PEPT, we conducted a pilot study at the UMC St Radboud Nijmegen.
      The results of this pilot study were very promising and therefore, we decided to design a
      large RCT to investigate the treatment effects and costs in CRPS patients treated with PEPT
      compared to CRPS patients treated with usual therapy according to the Dutch CBO guidelines.

      Study design:

      Prospective, single-blinded, randomized clinical trial. After base-line measurements (T0),
      measurements are performed at three (T1) and six months (T2) after inclusion. Follow-up is at
      nine months (T3).

      Study population:

      Patients with Complex Regional pain Syndrome (CRPS-1) of either upper or lower extremity
      according to Bruehl's/IASP criteria (see attachment) between 3 and 24 months after initial
      injury will be selected for the study. After information about standard and experimental
      treatments for CRPS and after informed consent, patients will enter the study and
      randomization for usual (CBO) or experimental (PEPT) treatment will be performed.

      Intervention:

      Treatment group: In the treatment group medication prescribed for CRPS is tapered to zero. No
      invasive treatments like sympathetic blocks, and/or operations will be performed. After
      information about the mechanism of action of PEPT in relation to CRPS, patients receive five
      sessions of PEPT including homework exercises. The basic of PEPT is a function-oriented
      exercise therapy. The PEPT physical therapist manipulates restricted joints and intensively
      trains functional skills irrespective of pain experience during or after the therapy.
      Patients are stimulated to use an active coping style to achieve a clear functional goal in 5
      sessions.

      Control group: Usual treatment of CRPS according to the Dutch CBO CRPS guideline 2006
      including, analgesics (WHO pain ladder), neuropathic drugs, N-acetylcysteine, calcium channel
      blocker, ketanserin and DMSO (dimethylsulphoxide). On indication, percutaneous sympathetic
      blocks or spinal cord stimulation will be performed. In addition, patients receive physical
      therapy with exercises within pain limits (pain contingent), splints and if necessary, aids
      for ADL activities.

      Outcome measures:

      Primary outcome measure is the Impairment level SumScore (ISS), which consists of three
      measurement parameters (pain, active range of motion and temperature) and four measurement
      instruments (VAS, McGill Pain Questionnaire, goniometry of mobility of joints and skin
      thermometer). A cost-effectiveness analysis from a societal perspective comparing PEPT to
      usual care in patients with CRPS will be performed. This will be done along-side the clinical
      trial.

      Sample size calculation/data analysis:

      The sample size calculation is based on the following finding and expectation. The
      improvement in ISS (primary outcome) over one year for the standard physical therapy group
      was 50% [Oerlemans, APMR 2000], for the PEPT group it is estimated at minimal 70-80%. Given
      an alpha of 0,05 and a power of 80% for a one sided Chi-square test 31 patients are needed
      per group. The Student T- test is used to calculate differences between both groups in mean
      ISS.
    

Intervention name(s): PEPT; CBO standard
Intervention type(s): Procedure; Procedure
Intervention description(s): Pain Exposure Physical Therapy; Standard therapy as defined in CBO guideline 2006
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Complex Regional Pain Syndrome Type I; Sympathetic Reflex Dystrophy; Pain Exposure Physical Therapy; Pharmacological treatment; Functional recovery