Condition category
Musculoskeletal Diseases
Date applied
09/01/2006
Date assigned
09/01/2006
Last edited
18/08/2009
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr J.J. Hilten, van

ORCID ID

Contact details

Leiden University Medical Center
Department of Neurology
Postzone K-05Q
P.O. Box 9600
Leiden
2300 RC
Netherlands
+31 (0)71 5262134
j.j.van_hilten.neurology@lumc.nl

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

NTR499; P05.108

Study information

Scientific title

Acronym

The ITG study (ITG is an abbreviation for intrathecal glycine)

Study hypothesis

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

Received from local medical ethics committee

Study design

Randomised double blind placebo controlled crossover group trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Condition

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

Phase

Not Specified

Drug names

Primary outcome measures

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).

Secondary outcome measures

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

Overall trial start date

21/11/2005

Overall trial end date

21/11/2007

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

20

Participant 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)

Recruitment start date

21/11/2005

Recruitment end date

21/11/2007

Locations

Countries of recruitment

Netherlands

Trial participating centre

Leiden University Medical Center
Leiden
2300 RC
Netherlands

Sponsor information

Organisation

Leiden University Medical Centre (Netherlands)

Sponsor details

Department of Neurology
P.O. Box 9600
Leiden
2300 RC
Netherlands

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

Ministry of Economic Affairs (Netherlands)

Alternative name(s)

Ministry of Economic Affairs, Netherlands Ministry of Economic Affairs, EZ

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

Netherlands

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2009 results in http://www.ncbi.nlm.nih.gov/pubmed/19683392

Publication citations

  1. Results

    Munts AG, van der Plas AA, Voormolen JH, Marinus J, Teepe-Twiss IM, Onkenhout W, van Gerven JM, van Hilten JJ, Intrathecal glycine for pain and dystonia in complex regional pain syndrome., Pain, 2009, 146, 1-2, 199-204, doi: 10.1016/j.pain.2009.07.030.

Additional files

Editorial Notes