Intrathecal Baclofen Infusion for Reflex sympathetic Dystrophy related dystonia

ISRCTN	ISRCTN43633981
DOI	https://doi.org/10.1186/ISRCTN43633981
Protocol serial number	P01.098; NTR403
Sponsor	Leiden University Medical Centre (LUMC) (The Netherlands)
Funders	Leiden University Medical Centre (LUMC) (The Netherlands), Medtronic Europe S.A. (Switzerland)

Submission date: 26/02/2007
Registration date: 26/02/2007
Last edited: 15/10/2008

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

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof J J van Hilten
Scientific

Leiden University Medical Centre (LUMC)
Department of Neurology
Postzone K-05Q
P.O. Box 9600
Albinusdreef 2
Leiden
2300 RC
Netherlands

Phone	+31 (0)71 526 6065
Email	J.J.van_Hilten@lumc.nl

Study information

Primary study design	Interventional
Study design	Part one: a single blinded placebo-run-in, dose-escalation design Part two: thereafter, in responders, an open trial
Secondary study design	Single-centre
Scientific title
Study acronym	The BIRD study
Study objectives	Dystonia associated with reflex sympathetic dystrophy responds markedly to intrathecal baclofen (ITB).
Ethics approval(s)	Approval received from the local ethics committee (Commissie Medische Ethiek) on the 2nd November 2001 (ref: P01.098).
Health condition(s) or problem(s) studied	Reflex sympathetic dystrophy (RSD)
Intervention	Screening phase: To evaluate the efficacy of ITB a percutaneous catheter is introduced into the lumbar subarachnoid space. All patients will start with a two-day placebo run-in, followed by a gradual titration of continuous intrathecal baclofen through an external pump. The daily baclofen dose will be increased according to a fixed schedule (200, 250, 300, 375, 450, 500, 600, 700 and 800 µg/24 hours). Depending on the response, the duration of the screening procedure may vary from one to two weeks. If a baclofen-related side-effect occurs at a particular dose, then depending on the severity of the side-effect the pump will be stopped or adjusted to a lower infusion rate. The outcome that is evaluated to determine if a patient will be implanted is the difference in change between Global Dystonia Severity (GDS - Visual Analogue Scale on which symptom severity is rated from zero [absent] to ten [most severe]) on ITB and placebo days. This difference is calculated through the following steps: 1. GDSbaclo: for each ITB day the sumscore of six one-hour intervals (11.00 a.m. - 4.00 p.m.) is determined. Likewise, for the two placebo days a mean placebo-sumscore is calculated (GDSplacebo) 2. GDShome: a similar mean sumscore of six one-hour intervals of the GDS at home is determined 3. For each day the GDS change score is calculated as follows: GDSbaclo - GDShome = GDSchangescore1, expressed in % (calculated for each ITB day) GDSplacebo - GDShome = GDSchangescore2, expressed in % (calculated for the mean of the two placebo days) Criteria for being a candidate for pump implantation: a greater than or equal to 25% difference between the GDSchangescore1 and GDSchangescore2 present on two subsequent days (responder). Implantation phase: After the screening phase a programmable pump (SynchroMed Infusion system, Medtronic INC, Minneapolis MN) for continuous ITB administration will be implanted in patients who fulfill the criteria stated above. During this phase ITB therapy will be started at a dose double the effective screening dose and will be titrated for a maximum effect over a three-month period. All implanted patients will be co-managed by the department of rehabilitation. Following implantation, severely affected patient will be referred to an in-patient rehabilitation unit. Mild to moderately affected patients will be seen in the out-patient rehabilitation unit.
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Intrathecal baclofen (ITB)
Primary outcome measure(s)	1. GDS will be calculated separately at baseline (GDShome) and during a week at one year of follow-up. The difference between these two measurements is identified as the change from baseline in GDS at one-year follow-up (GDS1year) 2. Dystonia related Functional Limitations (DFL) are self-assessed at hourly intervals across the day using four items, addressing upper extremity function, capability of making transfers and mobility. Each item is assessed on a zero to three scale. DFL will be calculated at baseline (DFLhome) and during a week at one year of follow-up. The difference between these two measurements is identified as the change from baseline in DFL at one year follow-up (DFL1year).
Key secondary outcome measure(s)	1. RSD related impairments 2. Activities of Daily Living (ADL) and quality of life will be assessed separately before implantation and at one-year follow-up The difference between these two measurements is identified as the change from baseline for each score.
Completion date	01/01/2006

Eligibility

Participant type(s)	Patient
Age group	Not Specified
Sex	Not Specified
Target sample size at registration	45
Key inclusion criteria	1. All patients should fulfill the diagnostic criteria of the complex regional pain syndrome consensus report of the International Association for the Study of Pain (IASP): 1.1. Continuing pain, allodynia or hyperalgesia, in which the pain is disproportionate to any inciting event 1.2. Evidence at some time of oedema, 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. All patients must suffer from tonic dystonia in one or more extremities, that may cause fixed postures at rest of variable severity 3. Before starting the study all patients will have received a trial with oral baclofen. Only patients with an insufficient response or dose-limiting sedative effects to oral baclofen are eligible for this study
Key exclusion criteria	Does not comply with the above inclusion criteria
Date of first enrolment	01/01/2002
Date of final enrolment	01/01/2006

Locations

Countries of recruitment

Netherlands

Study participating centre

Leiden University Medical Centre (LUMC)

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