Study to Evaluate the Efficacy and Safety of Lenalidomide in the Treatment of Complex Regional Pain Syndrome Type 1
Condition: Complex Regional Pain Syndrome, Type I
MeSH terms: Complex Regional Pain Syndromes; Reflex Sympathetic Dystrophy; Syndrome; Somatoform Disorders
Intervention: lenalidomide; Placebo
Intervention description: Two 5 mg capsules taken one time per day; Two placebo capsules taken one time per day
Intervention MeSH terms: Lenalidomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 184.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: CRPS; RSDS; Pain; CC-5013; Revlimid; Complex Regional Pain Syndrome; Reflex Sympathy Dystrophy Syndrome; Lenalidomide; CRPS Type I; Celgene

Summary:

      The purpose of this multicenter, double-blind, placebo-controlled study is to evaluate the
      efficacy and safety of Lenalidomide in adult subjects with Complex Regional Pain Syndrome
      (CRPS) Type 1.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age >= 18 years at the time of signing the informed consent form

          -  Understand and voluntarily sign an informed consent form

          -  A diagnosis of CRPS Type 1, as defined by modified International Association for the
             Study of Pain criteria for at least a one-year duration. Unilateral involvement of a
             distal limb (hand or foot) with or without proximal spread must be present. In the
             presence of upper and lower limb involvement, the most severely affected limb will be
             designated the CRPS-affected limb.

          -  Screening: CRPS pain intensity score in the CRPS-affected limb must be at least 4 on
             an 11-point (0-10) Pain Intensity Numerical Rating Scale (PI-NRS).

          -  Randomization: Average PI-NRS score for randomization purposes will be based on AM and
             PM assessments made during the 7 days prior to randomization. At least eight PI-NRS
             scores during this 7-day period are required and the Average PI-NRS score in the
             CRPS-affected limb during this period must be at least 4 on an 11-point (0-10) PI-NRS.

          -  Measurable (by electrophysiology methods) sural, median sensory, median motor and
             peroneal motor nerves at the screening nerve conduction study.

          -  Opioid analgesics, non-opioid analgesics, non-steroidal anti-inflammatory drugs,
             anticonvulsants, antidepressant drugs and other non-drug therapies may be continued
             provided that the subject is on stable doses/regimens for at least four weeks prior to
             the start of the Treatment Phase (Visit 2).

          -  Able to adhere to the study visit schedule and other protocol requirements.

          -  Women of childbearing potential (WCBP) must agree to practice complete abstinence from
             heterosexual intercourse or to use two methods of contraception beginning 4 weeks
             prior to the start of study drug (Day 1) while on study drug (including dose
             interruptions) and 4 weeks after the last dose of study drug. The two methods of
             contraception must include one highly effective method (i.e. intrauterine device
             [IUD], hormonal [birth control pills, injections, or implants only if used in
             conjunction with a low-dose (81 mg/day) aspirin regimen], tubal ligation, partner's
             vasectomy) and one additional effective (barrier) method (i.e. latex condom,
             diaphragm, cervical cap). If a hormonal method (birth control pills, injections, or
             implants) or IUD is not medically possible for the subject, two of the barrier methods
             will be acceptable.

          -  Women of childbearing potential (WCBP) must have two negative pregnancy tests
             (sensitivity of at least 50 mlU/mL) prior to starting study drug treatment. The first
             test should be performed within 10-14 days and the second within 24 hours of starting
             study drug. Once treatment has started, it is recommended that subjects have weekly
             pregnancy test during the first 4 weeks of treatment. Thereafter, subjects are
             required to have pregnancy testing every 4 weeks in females with regular menstrual
             cycles and every 2 weeks in females with irregular cycles.

          -  Males (including those who have had a vasectomy) must use barrier contraception (latex
             condoms) when engaging in reproductive sexual activity with WCBP while on study drug
             and for 4 weeks after the last dose of study drug.

        Exclusion Criteria:

        The presence of any of the following will exclude a subject from study enrollment:

          -  History of deep vein thrombosis (DVT) or stroke in the past 5 years.

          -  Documented peripheral neuropathies to include diabetic neuropathy and other metabolic
             or toxic neuropathies.

          -  Current signs or symptoms of severe, progressive or uncontrolled renal, hepatic,
             hematological, endocrine, pulmonary, cardiac, neurological or cerebral disease.

          -  Any other serious medical condition, laboratory abnormality, or psychiatric illness
             that would prevent the subject from signing the informed consent form.

          -  White blood cell count (WBC) < 3.5*10^9/L at screening.

          -  Bilirubin, alanine transaminase (ALT), aspartate transaminase (AST) or alkaline
             phosphatase levels more than two times the upper limit of the normal range at
             screening.

          -  Abnormal thyroid function test values at screening.

          -  Any condition, including the presence of laboratory abnormalities, which places the
             subject at unacceptable risk if he/she were to participate in the study or confounds
             the ability to interpret data from the study.

          -  Use of concomitant medication(s), which could increase the risk for developing DVT,
             except for steroid-based contraceptives (oral injectable, implantable) and hormone
             replacement therapies only if used in conjunction with a low-dose (81 mg/day) aspirin
             regimen.

          -  Concurrent use of thalidomide.

          -  Prior development of an allergic reaction/hypersensitivity while taking thalidomide.

          -  Prior development of a moderate or severe rash or any desquamation while taking
             thalidomide.

          -  Prior treatment with lenalidomide.