The effect of intrathecal methylprednisolone on features of central sensitisation in patients with chronic complex regional pain syndrome (CRPS) type one

ISRCTN	ISRCTN01838427
DOI	https://doi.org/10.1186/ISRCTN01838427
Protocol serial number	BSIK03016; NTR61
Sponsor	Leiden University Medical Centre (LUMC) (The Netherlands)
Funder	Ministry of Economic Affairs (The Netherlands)

Submission date: 23/01/2006
Registration date: 23/01/2006
Last edited: 04/06/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Signs and Symptoms

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr J J van Hilten
Scientific

Leiden University Medical Centre
Department of Neurology
Postzone K-05Q
P.O. Box 9600
Leiden
2300 RC
Netherlands

Phone	+31 (0)71 526 2895
Email	j.j.van_hilten.neurology@lumc.nl

Study information

Primary study design	Interventional
Study design	Randomised, placebo-controlled, double-blind, parallel group study
Secondary study design	Randomised controlled trial
Scientific title	The effect of intrathecal methylprednisolone on features of central sensitisation in patients with chronic complex regional pain syndrome (CRPS) type one
Study acronym	IMAC (Intrathecal Methylprednisolone And CRPS)
Study objectives	Intrathecal methylprednisolone reduce the features of central sensitisation in patients with complex regional pain syndrome (CRPS) type one having symptoms longer than six months and shorter than six years.
Ethics approval(s)	Ethics approval received from the local ethics committee
Health condition(s) or problem(s) studied	Chronic complex regional pain syndrome type 1 (CRPS I)
Intervention	In all patients a lumbar puncture will be performed. After a lumbar puncture 5 ml of fluid is removed for cytologic and biochemical tests. An additional 5 ml of fluid will be removed for the measurement of the level of cytokines. Then 60 mg of Depo-medrol® (methylprednisolone acetate) or placebo is injected. For patients whose pain is located in an arm the table will be tilted into the head-down position immediately after the intrathecal injection to allow the injected material to spread to the upper thoracic canal. Patients with symptoms in the lower extremities are kept in a horizontal position. Outcomes will be assessed six weeks after the intervention.
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Methylprednisolone acetate
Primary outcome measure(s)	The severity of spontaneous pain is evaluated through a 10 cm visual analogue scale (0 cm represents no pain, 10 cm represents the worst imaginable pain). This will be filled in at home in a diary. Primary outcome is pain relief at six weeks.
Key secondary outcome measure(s)	1. Sensory assessments: 1.1. The nature of the pain is assessed by means of the neuropathic pain scale developed by Galer which consists of several visual analogue scales for different kinds of pain. Also a McGill Pain Questionnaire will be administered 1.2. Hyper- and hypo-esthesia and allodynia will be tested using Von Frey hairs 1.3. Pain and temperature perception thresholds (Temperature Sensory Assessment using the Medoc TSA II Neurosensory Analyser). A thermode will be placed on the volar side of the wrist or dorsal side of the foot 1.4. Somatosensory evoked potentials 2. Autonomic assessments: 2.1. Skin temperature of affected and contralateral extremity and midsternal 2.2. The difference in volume between the affected and contralateral extremity is assessed by a volumeter as a measure for edema. This instrument measures the amount of water that is displaced by the immersed body part 2.3. Pulse transit time (the time the pulse wave takes to travel from heart to finger) as a measure of peripheral vessel resistance 3. Motor assessments: 3.1. Patients will be evaluated for the presence and severity dystonia, myoclonus and tremor (none, intermittent, continuous) 3.2. Range of motion will be assessed using a universal goniometer 3.3. In those patients in which this can be evaluated, movement velocity of repetitive fingertaps will be objectively quantified 3.4. In those patients in which this can be evaluated, proprioceptive reflexes will be assessed using a wrist pertubator 4. Disability: 4.1. Patients will be asked to mark the change in function of the affected hand or foot on a scale from one to seven (one = maximal worse, four = no change, seven = maximal better) 4.2. Radboud skills questionnaire, walking stairs questionnaire and questionnaire rising and sitting down will be administered 4.3. Participation and global health will be assessed using the Short Form (SF-36)questionnaire, EuroQol 5D questionnaire, Inventarisatielijst Sociale Betrekkingen (ISB) and Impact on Participation and Autonomy (IPA) 5. (Serious) adverse events
Completion date	01/02/2008

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	80
Total final enrolment	42
Key inclusion criteria	Patients will be male or female, outpatients aged 18 to 75 years, with a clinical diagnosis of CRPS who are referred to the Leiden University Medical Centre (LUMC): 1. At onset patients must fulfill the criteria for CRPS I. These criteria include: 1.1. The combination of continuing pain 1.2. Allodynia or hyperalgesia 1.3. Rendering the pain disproportionate to any inciting event 1.4. Evidence at some time of oedema 1.5. Changes in skin blood flow 1.6. Abnormal sudomotor activity in the region of the pain 1.7. Absence of a condition which would otherwise account for the degree of pain and dysfunction 2. When entering the study patients must suffer from symptoms and signs indicative of central sensitisation (continuing pain, hyperalgesia and/or allodynia) 3. Patients must have symptoms for more than six months and shorter than six years 4. Use of pain medication must have been stable in the previous four weeks 5. Patients must be willing and able to give informed consent according to the national requirements 6. Patients must report spontaneous pain of at least 5 cm on a visual analogue scale (0 cm represents no pain, 10 cm represents the worst imaginable pain)
Key exclusion criteria	1. Patients are excluded if they can obtain satisfactory relief of symptoms with conventional treatments such as non-steroidal anti-inflammatory drugs (NSAIDs) or paracetamol 2. Patients using oral anticoagulant medication or having an impaired blood coagulation for other reasons 3. Patients suffering from diabetes mellitus 4. Patients with an immunocompromised state 5. Patients with an acute infection 6. Patients with an intracranial space occupying lesion 7. Patients with a thrombocytopenia of less than 50 x 10^9/l 8. Patients with clinically significant psychiatric illness 9. Patients who have a history of alcohol or drug abuse within the past year 10. Patients with a known hypersensitivity to (methyl)prednisolone 11. Patients who are unlikely to comply with study requirements or have a history of poor compliance to medical regimens or study requirements 12. Patients who have received an experimental treatment within the last month 13. Pregnant, nursing women and females of childbearing potential not using oral contraceptives or a medically recognised mechanical means of contraception 14. Patients involved in legal proceedings (claiming compensation for the CRPS I)
Date of first enrolment	01/08/2005
Date of final enrolment	01/02/2008

Locations

Countries of recruitment

Netherlands

Study participating centre

Leiden University Medical Centre

Leiden
2300 RC
Netherlands

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/05/2010	04/06/2019	Yes	No

Editorial Notes

04/06/2019: Total final enrolment and publication reference were added.