Effectiveness of High-frequency Specific Speech Therapy on Verbal Fluency Decline and/ or Verbal Apraxia in Patients With Parkinson's Disease With and Without Deep Brain Stimulation (DBS) - a Randomized Controlled Single-blinded Trial
Phase: NA
Conditions: Parkinson's Disease
Sponsor: University Hospital, Basel, Switzerland

 
 
Dept. Clinical Neurophysiology/ Neurology 
 
 
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Clinical Study Protocol 
 
 
 
Title:   
 
Effectiveness of specific and intensive speech-language therapy on verbal fluency decline and 
verbal apraxia symptoms in patients with Parkinson’s disease with and without Deep Brain 
Stimulation (DBS) – a randomized single-blind controlled trial. 
 
Acronym:  
EILT (Evaluation of Intensive Language Therapy) 
 
 
 
 
EKNZ Nr: 
2016-01 428  
 
 
 
 
Clinicaltrail.gov. NR: NCT 029 358 42           
 
 
 
 
 
Document Created: 
 
 
30.11.2015 
 
Ethical Approval Obtained: 
 
13.09.2016 
 
Study Start/ First Patient IN: 
 
19.09.2016 
Last Patient OUT: 
 
 
29.06.2018 
 
Study End: 
 
 
 
22.10.2018 
 
 
Final Document update: 
 
09.10.2019 

 
 
Dept. Clinical Neurophysiology/ Neurology 
 
 
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Study Synopsis 
1. Background 
and Rationale: 
In the course of Parkinson’s disease (PD) speech and language (SL) deficits may 
often emerge. In addition, severe verbal fluency (VF) decline has been repeatedly 
observed in the context of deep brain stimulation (DBS) in PD. While PD non-DBS 
patients have deficits with respect to loudness and intelligibility of their voice, PD 
patients who have undergone DBS (PD-DBS) tend rather to suffer from difficulties in 
semantic and phonemic word retrieval, and from speech apraxia symptoms. However, 
to-date and to the best of our knowledge, therapeutic approaches focusing specifically 
on SL deficits observed in PD-DBS patients are yet to be developed and evaluated 
regarding their effectiveness.  
2. Objective(s): 
To evaluate the effectiveness of a high frequency and specific SL therapy compared 
to an unspecific, non-verbal sham intervention (rhythmic balance-mobility-training 
(rBMT)), as well as to a ‘no therapy’-condition.  
In more detail:  
(1) To compare rhythmic speech and gait of PD-DBS and PD non-DBS patients 
after different intensive rhythmic intervention programs (rSLT, rBMT and no 
therapy), as well as against healthy controls (HC) directly after the 
intervention and again in 6 months (short and long-term effects). 
 
Secondary objectives: 
(1) To examine how speech and language abilities alter due to Parkinson 
Disease’s (PD) by comparing PD-DBS, PD non-DBS and HC (all groups are 
age-, gender and education-matched).  
(2) To examine the effect of rhythmic interventions on cognitive abilities. 
(3) To evaluate measures derived from functional Near Infrared Spectroscopy 
(fNIRS) as a prognostic marker for verbal and cognitive outcome in PD 
patients with and without DBS over a period of time. 
3. Outcomes 
 
Primary study outcome: rhythmic abilities in speech and gait (Velocity and Cadence). 
 
Secondary study outcome: 
• Evaluating the effect of rhythmic interventions on cognition. 
• Evaluating cortical hemodynamic responses in PD and healthy elderly using 
functional near-infrared spectroscopy (fNIRS) 
4. Study 
Design: 
Investigator-blinded; Randomized; Controlled; Cross-over. 
 
 
 
 
 
 
 
 
 
 

 
 
Dept. Clinical Neurophysiology/ Neurology 
 
 
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5. Recruitment  
Inclusion Criteria for all groups 
a) 
The patient is able to cooperate 
b) 
The patient has the mental competence to provide informed consent to participate in the 
study 
c) 
The patient speaks and understands German 
d) 
The participants are aged between 45-80 yrs. old. 
 
Specific Inclusion Criteria for the DBS Group 
a) 
Fulfilling the above stated inclusion criteria as stated in a, b, c and d above 
b) 
The patient is responsive to L-DOPA 
c) 
Having received or being scheduled for DBS  
 
Exclusion Criteria for all groups  
a) Severe psychiatric disease difficult to treat (compulsive disorder, depression, mania, psychosis, 
anxiety as outlined in ICD-10 (WHO 2015, current version). 
b) Patient with dementia (DMS-V, MMS<24, MoCa <21)  
c) Secondary Parkinsonism  
d) Age ≤18 years  
e) Pregnancy (early onset) 
f) Presence of a known disease other than PD that shortens the life expectancy  
g) Mental incompetence to provide informed consent to participate in the study  
h) Previous intracranial surgery 
i) Epilepsy 
j) Contraindications for DBS seen in MRI-scan (malignant tumors, severe micro vascular disease) 
k) Insufficient skills of German language for participating in neuropsychological evaluations 
l) Sensory problems, severe enough to significantly interfere with neuropsychological assessment 
m) Alcohol and/or drug addiction 
 
 
5.1 Number of 
Participants 
with Power 
Analysis: 
The intended sample size of Ntotal = 70 is based on a small effect size (η2=.25, which 
is statistically significant increase in the elicitation of words within a certain time) and 
has been calculated via the statistical programme g*power (power analysis published 
by the University of Düsseldorf). Further, we expect about 5 drop-outs. Thus, the 
intended total sample size (N=70) may compensate for any possible drop-outs, 
regardless of group type. 
 
 
6. Randomization 
 
 
Group 1+2+3 were randomized 1:1:1. As a cross-over designed study, PD patients could swap 
groups once a therapy- tranche has successfully been completed (i.e. BL, intensive therapy, 4 
weeks Follow-up, 6 months Follow-up assessments), see Figure 1. 
Group 4 were healthy elderly, who did not receive any therapy and participated once.   
 
 
Group 1:  
rhythmic Speech language Therapy (rSLT) 
 
Group 2:  
rhythmic Balance-Mobility Training (rBMT) 
 
Group 3: 
‘Waiting List’, PD patients receiving no therapy 
 
Group 4: 
Healthy Controls (HC) 

 
 
Dept. Clinical Neurophysiology/ Neurology 
 
 
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Figure 1. Study Design 
 
 
7. Testing 
 
 
Testing took place at baseline (BL), at 4 weeks  (T1, directly after the end of intensive treatment) 
and at 6 months (T2 Follow-up). 
 
a. Medical Examination (only at Baseline) 
 
i. 
Medical Examination regarding PD-dementia  
ii. 
Drug/Alcohol Abuse 
iii. 
Weight, Heigth, BMI 
iv. 
Medications 
v. 
UPDRS – Unified Parkinson’s Disease Rating Scale-I (1/1) 
vi. 
Modified Neurologic Examination according to Hoehn & Yahr 
vii. 
Falls Efficiency Scale-1 (FES-1)  
 
i. 
Speech-Language Tests with simultaneous PRAAT Recording (BL, T1, T2) 
i. 
Reading ‘the northwind and the sun’  
ii. 
Aachner Aphasia Test (AAT): Spontaneous speech 
iii. 
AAT: Repeating 
iv. 
AAT: Naming 

 
 
Dept. Clinical Neurophysiology/ Neurology 
 
 
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v. 
Regensburgerwortflüssigkeitstest (RWT) complete 
vi. 
Comprehension of language-specific cues (Gardenpath Experiment)  
 
b. Motor Tests 
• One-leg and Tandem standing test (timed via chronometric stop watch in seconds) 
• Parkinson Orientated Mobility Assessment (POMA) 
• Walking 6 Meters (timed and counting steps) 
 
c. Near-Infrared Spectroscopy (NIRS) (only at BL) 
 
d. Neuropsychological tests/ psychiatric questionnaires (BL, T1 and T2) 
 
 
Neuropsychological Tests: 
i. 
MOCA – Montreal Cognitive Assessement 
ii. 
Clock Test 
iii. 
CERAD – Boston Naming Test 
iv. 
CERAD – Word Retrieval (Animals) 
v. 
BVLT – Basel Verbal Learning Test 
vi. 
BVLT – Basel Verbal Learning Test 
vii. 
ROCF - Rey-Osterrieth Complex Figure 
viii. 
BVLT - Basel Verbal Learning Test 
ix. 
BVLT - Basel Verbal Learning Test - Recognition  
x. 
Word retrieval (S-Words) 
xi. 
TMT - Trail Making Test A 
xii. 
Trail Making Test B  
xiii. 
Stroop Test 
xiv. 
WMS-R - Verbal Digit Span 
xv. 
WMS-R - Corsi Blocks 
xvi. 
Mosaik-Test  
xvii. 
BVMT-R – Brief Visuospatial Memory Test-Revised  
xviii. 
TAP – Alertness  
xix. 
TAP - Divided Attention  
xx. 
Delayed Recall BVMT-R 
xxi. 
Recognition BVMT-R 
xxii. 
Tulia 
 
 
Psychiatric Self-Rating Questionnaires: 
ii. 
BDI – Beck’s Depression Inventory (1/2) 
iii. 
BAI – Beck Angst (Fear) Inventar 
iv. 
MSS – Manie-Selbstbeurteilungsskala (Mania) (1/2) 
v. 
OCIR – Obsessive-Compulsive Inventory-Revised 
vi. 
BIS-11 – Barrat-Impulsiveness-Scale (1/2) 
vii. 
PDQ-39 – Parkinson Quality of Life Questionnaire  
viii. 
NEO-FFi-30 Items  

 
 
Dept. Clinical Neurophysiology/ Neurology 
 
 
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ix. 
AES-S – Apathy Evaluation Scale  
x. 
PFS-16 –  Parkinson-Fatigueskala  
xi. 
Lebensqualitätsfragebogen (SeiQol-DW)  
xii. 
IQ-Code – Questioannaire of cognitive abilites in elderly 
 
8. Interventions 
 
No drugs involved. While speech-language therapy is an established intervention programme in 
clinical and therapeutic practices, the rhythmic balance-mobility-training (rBMT) has been 
developed specifically to prevent mobility and balance issues in PD patients and has been 
evaluated scientifically (see Parkinson Schweiz 
http://www.redance.ch/page/wirkung/sturzpraevention.html). 
Note that whether or not DBS is performed on a patient is dependent on multiple criteria and can 
only be decided by the medical team consisting of neurologists, neurosurgeon and 
neuropsychologists/ psychiatrists. Whether or not DBS is performed on a patient is not part of the 
study, as it is a normal medical procedure to cure dyskinesia and other motor symptoms arising in 
Parkinson’s disease. 
 
rSLT 
Contents 
 
I. 
3x 45 Minute sessions per week 
II. 
Empathic relationship between patient-therapist 
III. 
Specific exercises for the perception and improvement of 
respiration, phonation, articulation and body posture  
IV. 
Rhythmic Exercises according to ‘Accent Method’ by Sven Smith 
(1935, 1976) 
 
rBMT 
Contents 
 
• 3 x 45 minute sessions per week. 
• per session: at least 10 songs had to be danced, each with a length ranging 
from 1:47 - 3:25 Minutes per song. 
• 1st Week: Level 1. 
• 2nd Week: Level 1+2.  
• 3rd Week: Level 2. 
• 4th Week: Level 2+3.  
 
 
 
 
 
 

EILT – Evaluation of Intensive Language Therapy 
EKNZ NR: 2016- 01 428 
Clinicaltrail.gov ID: NCT02935842 
 
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7. Statistical Analysis 
 
To calculate group differences (i.e. rSLT, rBMT, NT, HC) several univariate ANOVA with post-hoc 
Bonferroni corrections were performed.  
Relationships between speech and gait variables were computed with Spearman’s correlations 
(significance level p < .05). The level of statistical significance was set at p < .05. 
Changes in performance were analyzed with the reliable change score (RC). According to Jacobson and 
Truax (1991) scores are compared on a participant-individual level (e.g. BL with 4 weeks FU, and BL with 
6 months FU). Positive scores indicate an improvement in performance, and negative scores indicate a 
worsening of performance. The RC shows whether a difference in performance is statistically significant 
on the basis of the reliability of the measurement. Thus, the reliable change score is equivalent to 
computing a z-score based on standard deviation units.  
Further group comparisons are based on the RC scores. All statistical analyses were conducted with 
SPSS and R. All results are presented with effect sizes. 
 
7.1 Data Availability Agreement 
 
The Clinical Trail Unit (CTU) of the University Hospital Basel will act as a repository data system. Access 
to data is granted via formal research enquiry. 
 
 
8. GCP Statement: 
 
This study has been conducted in compliance with the protocol, the current version of the Declaration of 
Helsinki, the ICH-GCP or ISO EN 14155 (as far as applicable) as well as all national legal and regulatory 
requirements.  
 
9. Risks/ Inconveniences, which are study specific:  
 
As Parkinson Patients may suffer from dyskinesia (e.g. rigor, tremor and akinesia), which may affect their 
movement control and balance, the rhythmic balance-mobility training  (rBMT) may potentially put the 
patients at risk to fall during the intervention. However, there are scaffolds mounted to either side of the 
rBMT platform, onto which the patient will be holding on to. Furthermore, the research team and 
therapeutic team will monitor patients during the rBMT as well as the speech-language therapy in order to 
insure the patients’ safety. 
 
10. Benefit for the patient 
 
Through the course of PD patients, both, those who undergo DBS surgery and those who do not, suffer 
from different degrees of SL performance, which significantly restricts their communication in the society, 
daily leaving activities and overall quality of life. We anticipate developing and evaluating a possibly 
preventive or curative therapy considering the patients’ SL deficits.  
Further, this evaluation will help doctors treating PD patients as well as PD patients to inform 
(themselves) and choose the therapeutic approach in time regarding the patient’s specific needs.  
 
 

EILT – Evaluation of Intensive Language Therapy 
EKNZ NR: 2016- 01 428 
Clinicaltrail.gov ID: NCT02935842 
 
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Rationale for the estimated benefit/risk relationship for the patient: 
 
Since the speech-language testing and the interventions per se are non-invasive participating within this 
study is totally risk-free for the patients. Further, there will be no negative consequences whatsoever in 
case the patient wants to dropout of the study, and dropping-out of the study is possible at any time during 
the study. 
Further, participation in the study will also mean a thorough and fine-grained screening of the patient’s 
health condition (i.e. neurological, neurophysiological, neuropsychiatric and cognitive, etc.). Therefore, this 
high-frequency screening may allow detecting any concerning health problems early and will be discussed 
directly (if requested by the patient). In turn, this high-frequency contact with doctors gives the PD patient 
the rather unique chance to be well informed and ask questions at any time or raise important issues 
early. 
The interventions themselves are unique and specifically tailored to the needs and SL deficits as 
experienced by the PD-DBS or non-DBS patients. To-date, there is no other intervention program being 
more up-to-date with the research field than this one presented in this project. Thus, there beneficial effect 
is not proven. However, the gained insight of their effectiveness will help future PD patients and their 
neurologists, doctors to give accurate and evidence-proven information about alternative (non-medical) 
interventions or therapeutic methods,  
 
Selected References:  
 
Batens, K., De Letter, M., Raedt, R., Duyck, W., Vanhoutte, S., Van Roost, D. & Santens, P., 2014. The 
effects of subthalamic nucleus stimulation on semantic and syntactic performance in 
spontenous language production in people with Parkinson's disease. Journal of 
Neurolinguistics. 32: 31-41. 
Cantiniaux, S., Vaugoyeau, M., Robert, D., Horrelou-Pitek, C., Mancini, J., Witjas, T., Azulay, J.-P. (2010). 
Comparative analysis of gait and speech in Parkinson’s disease: hypokinetic or dysrhythmic 
disorders? Journal of Neurology, Neurosurgery and Psychiatry, BMJ Publishing Group, 2010, 
81 (2), pp.177.  
Ehlen, F. 2007. Effects of subthalamic Deep Brain Stimulation on dysarthria in Parkinsons disease 
Department of Medicine - Charité - University Medicine Berlin (unpublished Doctorate's 
thesis). 
Ehlen, F., Krugel, L.K., Vonberg, I., Schoenecker, T., Kühn, A.A., Klostermann, F., 2013. Intact lexicon 
running slowly--prolonged response latencies in patients with subthalamic DBS and verbal 
fluency deficits. PloS One 8, e79247.  
Ramig, L.O., Fox, C., Sapir, S., 2008. Speech treatment for Parkinson’s disease. Expert Rev. Neurother. 
8, 297–309.  
Riecker A1, Mathiak K, Wildgruber D, Erb M, Hertrich I, Grodd W, Ackermann H. 2005. fMRI reveals two 
distinct cerebral networks subserving speech motor control. Neurology. 22;64(4):700-6. 
Sarnthein, J. & Jeanmonod, D., 2007. High Thalamocortical Theta Coherence in Patients with Parkinson’s 
Disease. J Neurosci 27, 124–131.  
Skodda S. 2011. Aspects of speech rate and regularity in Parkinson's disease. J Neurol Sci. 15; 310(1-2): 
231-6.