Double-blind randomised placebo-controlled cross-over study to investigate the safety and effectiveness of intrathecal glycine on pain and dystonia in Complex Regional Pain Syndrome type 1

ISRCTN	ISRCTN75413193
DOI	https://doi.org/10.1186/ISRCTN75413193
Protocol serial number	NTR499; P05.108
Sponsor	Leiden University Medical Centre (Netherlands)
Funder	Ministry of Economic Affairs (Netherlands)

Submission date: 09/01/2006
Registration date: 09/01/2006
Last edited: 18/08/2009

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Musculoskeletal Diseases

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. Hilten, van
Scientific

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

Phone	+31 (0)71 5262134
Email	j.j.van_hilten.neurology@lumc.nl

Study information

Primary study design	Interventional
Study design	Randomised double blind placebo controlled crossover group trial
Secondary study design	Randomised controlled trial
Scientific title
Study acronym	The ITG study (ITG is an abbreviation for intrathecal glycine)
Study objectives	A large proportion of chronic patients with complex regional pain syndrome type 1 suffer from both neuropathic pain and dystonia. Findings from neurophysiological and intrathecal baclofen studies highlight an impaired inhibitory neurotransmission. Since glycinergic neurotransmission plays an important inhibitory role in afferent and motor processing, glycine administration may offer new options for the treatment of both pain and movement disorders in patients with CRPS I.
Ethics approval(s)	Received from local medical ethics committee
Health condition(s) or problem(s) studied	Complex regional pain syndrome type 1 (CRPS I)
Intervention	For future intrathecal baclofen treatment, in all patients a programmable pump for continuous intrathecal administration (SynchroMed® pump, Medtronic, Minneapolis MN, USA, 40 ml reservoir) and a lumbar reservoir for cerebrospinal fluid sampling will be implanted. Each subject receives two treatments: 1. 2.1% glycine solution during 4 weeks 2. Natrium chloride 0.9% during 4 weeks (placebo) Study treatment is started at a dosage of 8/21 ml/24 hours (during treatment with glycine 2.1% this corresponds to 8 mg/24 hours) and will be weekly increased with 8/21 ml/24 hours. There is a tapering and wash-out period after each treatment: tapering in 1 week (3 equal dose decreases with an interval of 48 hours e.g. Monday 22, Wednesday 12 and Friday 0 mg/24 hours) and wash-out in 1 week. Treatment is started on Mondays.
Intervention type	Other
Primary outcome measure(s)	Primary outcome is the safety of ITG. Safety evaluations include history taking, physical examination and neurological examination, blood and cerebrospinal fluid assessments and 12-lead electrocardiography (ECG).
Key secondary outcome measure(s)	Secondary outcome is the efficacy of ITG compared to placebo. Patients are assessed: 2 weeks before pump implantation, during both treatments at days 1, 8, 15, 22 and 29. At days of dose adjustment, assessments are performed first. These assessments include: 1. Movement disorders assessments: 1.1. Visual analogue (VAS) dystonia scale: self-assessed every Monday at 9:00, 14:00 and 20:00 from 2 weeks before pump-implantation to the end of the study. Symptom severity is rated from 0 (absent) to 10 (most severe). 1.2. Standardised measures are: 1.2.1. The Fahn-Marsden dystonia rating scale 1.2.2. Barry-Albright Dystonia scale 1.2.3. Unified myoclonus rating scale (sections 2, 3, 4, 5, 7 and 8) 1.2.4. Tremor research group rating scale Assessed 2 weeks before pump implantation and during both treatments at days 1, 8, 15, 22 and 29. 1.3. Change of dystonia is rated on a global impression scale. The blinded investigator assesses the change from baseline on a global impression scale at the end of both treatments. 2. Sensory assessments: 2.1. VAS pain scale: self-assessment (as VAS dystonia scale) 2.2. McGill pain questionnaire: assessed every Monday from 2 weeks before pump-implantation to the end of the study 2.3. Thermal sensory analyzer: to assess pain and temperature perception thresholds (Medoc Ltd, Israel, model TSA-II, using the method of limits) and is done during both treatments at days 1 and 29. A thermode is placed on the volar side of the wrists (if involved) and the dorsal side of the feet (if involved). 3. Activity level: 3.1. Radboud Skills Questionnaire: in case of involvement of upper extremities 3.2. Walking Ability Questionnaire: in case of involvement of lower extremities
Completion date	21/11/2007

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	20
Key inclusion criteria	1. Patients must fulfil the diagnostic criteria of the consensus report of CRPS I: 1.1. Continuing pain, allodynia or hyperalgesia, in which the pain is disproportionate to any inciting event 1.2. Evidence at some time of edema, changes in skin blood flow or abnormal sudomotor activity in the region of the pain 1.3. No condition that would otherwise account for the degree of pain and dysfunction 2. Patients must suffer from clinically significant tonic or intermittent dystonia in one or more extremities 3. Patients must have symptoms for at least 1 year
Key exclusion criteria	1. Patients are excluded if they can obtain satisfactory relief of symptoms with conventional treatments 2. Patients with a history of alcohol or drugs abuse within the past year 3. Patients with clinically significant psychiatric illness 4. Pregnant, nursing women and females of childbearing potential not using effective contraception 5. Patients who are unlikely to comply with study requirements or have a history of poor compliance to medical regimens or study requirements 6. Patients with an insufficient command and understanding of the Dutch language 7. Patients involved in legal proceedings (claiming compensation for their CRPS I)
Date of first enrolment	21/11/2005
Date of final enrolment	21/11/2007

Locations

Countries of recruitment

Netherlands

Study participating centre

Leiden University Medical Center

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	01/11/2009		Yes	No