Condition category
Nervous System Diseases
Date applied
28/05/2010
Date assigned
28/05/2010
Last edited
10/08/2016
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

Mr Sadaquate Khan

ORCID ID

Contact details

Frenchay Hospital
Frenchay Park Road
Bristol
BS16 1LE
United Kingdom
+44 117 41 49330
sadaquate.khan@nbt.nhs.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

4455

Study information

Scientific title

Deep brain stimulation of the pedunculopontine nucleus for Parkinson's Disease: a single centre randomised interventional treatment trial

Acronym

Study hypothesis

In patients with Parkinson's disease problems with balance, walking and speech are considered to be some of the most disabling symptoms. The symptoms are collectively known as axial symptoms. At present the available medical therapy and surgery, in the form of deep brain stimulation result in a limited improvement in axial symptoms especially in the later stages of this disease. Research work over the past 20 years has indicated that degeneration of an area in the brainstem, the pedunculopontine nucleus (PPN) may be involved in producing axial symptoms in Parkinson's disease. Work by Professor Aziz in Oxford has shown an improvement in axial symptoms in primate models of Parkinson's disease following stimulation of the PPN.

Following on from this work, our research group was one of the first to publish on deep brain stimulation of this area in patients with Parkinson's Disease. Our initial results have shown a significant improvement of not only axial symptoms but patients also reported improvement in other symptoms including appetite and concentration. Following the success of our early pilot cases we now intend to perform a formalised trial in order to:
1. Determine the safety and efficacy of deep brain stimulation of the pedunculopontine nucleus (PPN) in conjunction with stimulation of the caudal zona incerta (cZi) (conventional site of stimulation in Parkinson's Disease) in patients with medically refractory Parkinson's Disease who have predominant symptoms of postural instability and gait dysfunction both in the on and off medication states)
2. Obtain greater understanding of the mechanism by which deep brain stimulation of the PPN and cZi region results in clinical improvement by studying the changes in regional cerebral blood flow using positron emission tomography (PET) scanning and electrical activity at these two sites using temporary externalised cables and electroencephalogram (EEG) readings from the scalp in the post-operative period whilst stimulating these two regions separately and in combination

Ethics approval

South West 5 REC, 28/04/2006, ref: 06/Q2007/20

Study design

Single centre randomised interventional treatment trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Topic: Dementias and Neurodegenerative Diseases Research Network; Subtopic: Parkinson’s Disease; Disease: Parkinson's disease

Intervention

Following fully informed consent and surgical implantation of DBS electrodes to both the PPN and subthalamic region bilaterally, patients will enter into an initial 6 week period over which the Subthalamic region and PPN electrodes will be programmed individually and in combination in order to define the optimal settings for symptom control. At the end of the first 6 week period patients will be randomised into receiving deep brain stimulation at the predetermined optimal setting at either the Subthalamic region or the both the PPN and Subthalamic region simultaneously. This will occur for a further 6 - 12 week period at the end of which the primary and secondary outcome measures will be assessed. Following assessment of the outcome measures, patients will crossover to the other stimulator setting for a further 6 - 12 weeks. With two possible combinations of stimulator settings and an initial period used to define optimal stimulator settings the total duration of the trial will be 18 - 30 weeks.

Intervention type

Other

Phase

Phase II

Drug names

Primary outcome measures

Change in frequency of gait freezing, measured for 3 days in each condition and averaged.

Secondary outcome measures

1. Quality of life questionnaires (39-item Parkinson's Disease Questionnaire [PDQ-39] and 36-item Short Form Health Survey [SF-36])
2. The Unified Parkinson's Disease Rating Scale (UPDRS)
3. Change in concomitant antiparkinsonian medications
4. Neuropsychological assessment
5. Parkinson's Disease Non-Motor Symptoms Questionnaire
6. Timed walk, upper and lower limb movements and Purdue Pegboard
7. Tinetti balance and gait assessment tool

Measured pre-operatively and after each of the two randomisation settings (which could be at 12 - 18 weeks, or 18 - 30 weeks depending on how long the patient needs to be on each
stimulation setting in order to reach a stable clinical state on each of the stimulation settings.

Overall trial start date

22/10/2007

Overall trial end date

28/02/2011

Reason abandoned

Eligibility

Participant inclusion criteria

1. Diagnosis of advanced idiopathic Parkinson's disease poorly controlled on optimum medication with significant functional disability and predominant symptoms of postural instability and gait dysfunction in both the on and off medication states
2. They will have a Unified Parkinson's Disease Rating Scale (UPDRS) motor score of 30 or greater in their practically defined off condition at an initial evaluation. They will each show at least a 30% improvement in the UPDRS motor score from that of the practically defined off condition following a morning levodopa challenge.
3. At two preoperative evaluations the practically defined off UPDRS motor score should differ no more than +/- 15%
4. Subjects will be under the age of 70 years, either sex
5. Appropriate surgical candidate with no medical conditions that would interfere with long-term implantation of device and follow up
6. Patient must give signed informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned sample size: 8; UK sample size: 8

Participant exclusion criteria

1. Known current or past diabetes
2. Evidence of dementia, head trauma or medical conditions that may alter cerebral functioning
3. Past or present history of alcohol or substance abuse
4. Mini-mental state examination (MMSE) scores below 27 or above 30
5. Evidence of past or current serious psychopathology likely to affect the patients ability to benefit from surgery

Recruitment start date

22/10/2007

Recruitment end date

28/02/2011

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Frenchay Hospital
Bristol
BS16 1LE
United Kingdom

Sponsor information

Organisation

North Bristol NHS Trust (UK)

Sponsor details

Trust Headquarters
Beckspool Road
Frenchay
Bristol
BS16 1JE
United Kingdom

Sponsor type

Hospital/treatment centre

Website

http://www.nbt.nhs.uk/

Funders

Funder type

Industry

Funder name

Medtronic PLC

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

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

Publication citations

Additional files

Editorial Notes

10/08/21016: No publications found in PubMed, verifying study status with principal investigator.