Combined Deep Brain Stimulation in Parkinson's Disease
Condition: Parkinson Disease
MeSH terms: Parkinson Disease
Study type: Interventional

Summary: 
      The study is a pilot study on Parkinson's disease patients to evaluate Combined deep brain
      stimulation of the substantia nigra pars reticulata and of the subthalamic nucleus for
      unresponsive freezing of gait.
    

Detailed description: 
      One of the most challenging and unresolved problems in Parkinson's disease (PD) is the
      treatment of gait disorders, unresponsive to dopaminergic medication. Additionally, PD
      patients suffering from severe/unresponsive gait disorders are not considered good candidates
      for subthalamic nucleus deep brain stimulation (STN-DBS). Currently, there are no specific
      therapies to treat gait disorders in PD with an insufficient response to dopaminergic
      treatment. Furthermore, axial symptoms develop during disease progression even in operated
      patients. Axial symptoms are often one of the main causes of disability. There is evidence
      suggesting that low-frequency (LF) stimulation of the ventral area of the STN can improve
      axial symptoms. At the same time, the substantia nigra pars reticulata (SNr) is one of the
      most important output centers of the basal ganglia and is integrated within the locomotor
      control systems. Neurons within the SNr may act as high-frequency (HF) pacemakers, disrupting
      normal behavior downstream in the circuit. HF-STN in combination with LF or HF-SNr
      stimulation have been shown some beneficial effect on freezing of gait (FoG) among PD
      patients who had FoG unresponsive to dopaminergic therapy. However, only small pilot trials
      and case series have been investigated this strategy and evidences are scarce.

      The aim of this study is to evaluate the effect of combined (C) stimulation of the STN and
      SNr on FoG if compared to standard (S) stimulation of the STN at 130 Hz, over one month.
      Based on previous literature evidence as primary aim the respective effect of two setting of
      C-stimulation will be separately assessed: a) C1- stimulation, with HF stimulation of the STN
      and SNr using a 'interleaved pulses' at 125 Hz vs. S- stimulation, over one month; b)
      C2-stimulation with LF stimulation of the SNr at 60Hz and HF stimulation of the STN vs. S-
      stimulation, over one month.

      Other objectives are to evaluate the:

        -  Tolerance of combined stimulation (STN + SNr) through the collection of adverse events
           (AEs)

        -  Development of psychic events such as the presence of depression or dysphoria

        -  Effect of C (C1 and C2) -stimulation on walking disorders and other axial symptoms if
           compared vs. the S-stimulation.

        -  Effect of C (C1 and C2) -stimulation on PD's motor symptoms and motor complications if
           compared vs. the S-stimulation.

        -  Effect of C (C1 and C2) -stimulation on sleep quality if compared vs. the S-stimulation.

      Each patient will have the 3 types of stimulation:

        1. One month of S-stimulation (130hz, STN).

        2. One month of C1- stimulation;

        3. One month of C2- stimulation;

      Stimulation setting order will be randomly assigned. Minimal dopaminergic treatment
      adjustment will be allowed to minimize the drop-out rate (± 100 mg of levodopa equivalent
      daily dose) and registered
    

Intervention name(s): 1 : S-C1-C2; 2 : S-C2-C1; 3 : C1 - S - C2; 4 : C1 -C2 - S; 5 : C2 - S - C1; 6 : C2 - C1 - S
Intervention type(s): Device; Device; Device; Device; Device; Device
Intervention description(s): Deep brain stimulation of the substantia nigra pars reticulata and of the subthalamic nucleus according to the order of randomisation (see intervention name) :
Standard stimulation
125Hz at both STN and SNr for C1,
125Hz for STN and 60 for SNr for C2; Deep brain stimulation of the substantia nigra pars reticulata and of the subthalamic nucleus according to the order of randomisation (see intervention name) :
Standard stimulation
125Hz at both STN and SNr for C1,
125Hz for STN and 60 for SNr for C2; Deep brain stimulation of the substantia nigra pars reticulata and of the subthalamic nucleus according to the order of randomisation (see intervention name) :
Standard stimulation
125Hz at both STN and SNr for C1,
125Hz for STN and 60 for SNr for C2; Deep brain stimulation of the substantia nigra pars reticulata and of the subthalamic nucleus according to the order of randomisation (see intervention name) :
Standard stimulation
125Hz at both STN and SNr for C1,
125Hz for STN and 60 for SNr for C2; Deep brain stimulation of the substantia nigra pars reticulata and of the subthalamic nucleus according to the order of randomisation (see intervention name) :
Standard stimulation
125Hz at both STN and SNr for C1,
125Hz for STN and 60 for SNr for C2; Deep brain stimulation of the substantia nigra pars reticulata and of the subthalamic nucleus according to the order of randomisation (see intervention name) :
Standard stimulation
125Hz at both STN and SNr for C1,
125Hz for STN and 60 for SNr for C2
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Single center, randomized, three one-month periods, six sequences, cross-over, double blind, study to evaluate the effect of 2 innovative settings of DBS combining the stimulation of STN and SNr, vs. a standard (S) stimulation, on FoG, in PD patients with DBS with severe FoG.
the sequence of different stimulation parameters will be randomized and not the treatment Each patient receives the three treatments (S, C1 and C2)
Masking: Double (Participant, Investigator)
Primary purpose: Other
Keywords: freezing of gait; deep brain stimulation; combined deep brain stimulation