Clinical trial NCT00109772: Study to Evaluate the Efficacy and Safety of Lenalidomide in the Treatment of Complex Regional Pain Syndrome Type 1
Official title: A Multicenter, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Lenalidomide in the Treatment of Complex Regional Pain Syndrome Type 1
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Complex Regional Pain Syndrome, Type I
Keywords: CRPS
RSDS
Pain
CC-5013
Revlimid
Complex Regional Pain Syndrome
Reflex Sympathy Dystrophy Syndrome
Lenalidomide
CRPS Type I
Celgene
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2005-05-04
Enrollment: 184
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: This is a multicenter, double-blind, placebo-controlled study in adult subjects with Complex Regional Pain Syndrome (CRPS) Type 1.

One hundred eighty (180) subjects diagnosed with unilateral CRPS Type 1 will be enrolled and randomized to receive orally either 10 mg/day of lenalidomide or placebo (90 subjects per treatment arm). For each subject, the study consists of three phases: Pre-randomization Phase (2 weeks), Treatment Phase (12 weeks) and Extension Phase where subjects have the opportunity to receive lenalidomide treatment as long as a benefit is derived from the drug. Subjects who complete all 12 weeks of the treatment phase may be eligible to receive lenalidomide in the extension phase. Subject may continue in the extension phase as long as a benefit is derived from the drug.

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.

Primary outcomes:
measure: Percentage of Participants Who Have a >= 30% Reduction (Improvement) in the Complex Regional Pain Syndrome (CRPS) Pain Intensity Numeric Rating Scale (PI-NRS) Score From Baseline to the Last Assessment
timeFrame: Day 0, Week 12
Secondary outcomes:
measure: Change From Baseline in the Total Score of the Short Form McGill Pain Questionnaire (SF-MPQ) at Week 12
timeFrame: Day 0, week 12
measure: Change From Baseline in the Complex Regional Pain Syndrome (CRPS) Pain Intensity Numeric Rating Scale (PI-NRS) Score Using Averaged Morning and Evening Readings at Week 12
timeFrame: Day 0, week 12
measure: Change From Baseline in the Morning Complex Regional Pain Syndrome (CRPS) Pain Intensity Numeric Rating Scale (PI-NRS) Score at Week 12
timeFrame: Day 0, week 12
measure: Change From Baseline in the Evening Complex Regional Pain Syndrome (CRPS) Pain Intensity Numeric Rating Scale (PI-NRS) Score at Week 12
timeFrame: Day 0, week 12
measure: Change From Baseline in Daily Sleep Assessment Average Score at Week 12
timeFrame: Day 0, week 12
measure: Change From Baseline in Activity Level Rating Using a Numeric Rating Scale (NRS) at Week 12
timeFrame: Day 0, week 12
measure: Change From Baseline in Participant Assessment of CRPS Symptoms Total Score at Week 12
timeFrame: Day 0, week 12
measure: Change From Baseline in "Mechanically Evoked" (Allodynia) Numeric Rating Scale (NRS) Score at Week 12
timeFrame: Day 0, week 12
measure: Difference in Allodynia Rating Between the CRPS-affected Limb and the Normal Limb at Week 12
timeFrame: Week 12
measure: Change From Baseline in the Brief Pain Inventory (BPI) Total Score at Week 12
timeFrame: Day 0, week 12
measure: Change From Baseline in the Profile of Mood States (POMS) at Week 12
timeFrame: Day 0, week 12
measure: Patient Global Impression of Change (PGIC) at Week 12
timeFrame: Week 12
measure: Participants Who Had a Change to CRPS Pain Medication During the Treatment Period
timeFrame: Day 1 to week 12
measure: Change From Baseline in the Maximal Composite Motor Nerve Conduction Velocity at Week 12
timeFrame: Day 0, week 12
measure: Change From Baseline in the Maximal Composite Sensory Nerve Conduction Velocity at Week 12
timeFrame: Day 0, week 12
measure: Participants With Treatment-Emergent Adverse Events in the Double-Blind Period or the Extension Period
timeFrame: Day 1 up to week 158
Other outcomes:
Locations:
city: Peoria
country: United States
facility: Pivotal Research Centers
state: Arizona
city: La Jolla
country: United States
facility: UCSD Center for Pain and Palliative Medicine
state: California
city: Loma Linda
country: United States
facility: Loma Linda Institution
state: California
city: Palm Bay
country: United States
facility: Space Coast Neurology
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Rehab Institute of Chicago
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Medical Center
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: St. Louis
country: United States
facility: Washington University Pain Mgmt Ctr
state: Missouri
city: New York
country: United States
facility: Hospital for Joint Disease
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Chapel Hill
country: United States
facility: UNC Hospitals University of North Carolina
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Fort Bragg
country: United States
facility: Womack Army Medical Center
state: North Carolina
city: Winston Salem
country: United States
facility: Carolinas Pain Institute, P.A. & the Center for Clinical Research, LLC
state: North Carolina
city: Dayton
country: United States
facility: Research Institute of Greater Dayton
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Allentown
country: United States
facility: Lehigh Valley Hospital
state: Pennsylvania
city: Ft. Washington
country: United States
facility: Knobler Institute of Neurologic Disease
state: Pennsylvania
city: Philadelphia
country: United States
facility: Drexel University College of Medicine Department of Neurology Rm 7102
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Lubbock
country: United States
facility: Texas Tech Medical Center Department of Anesthesiology
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Pain Management Center
state: Virginia
city: Seattle
country: United States
facility: Swedish Pain Services
state: Washington
Study officials:
affiliation: Celgene Corporation
name: Donald C Manning, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Manning DC, Alexander G, Arezzo JC, Cooper A, Harden RN, Oaklander AL, Raja SN, Rauck R, Schwartzman R. Lenalidomide for complex regional pain syndrome type 1: lack of efficacy in a phase II randomized study. J Pain. 2014 Dec;15(12):1366-76. doi: 10.1016/j.jpain.2014.09.013. Epub 2014 Oct 2.