Clinical trial NCT01834911
Conditions: Huntington Disease
Keywords: Huntington disease HD tetrabenazine Stroop
Sponsor: New York Medical College
Start date: 2013-03-01; Completion date: 2018-01-01
Enrollment: 2 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Tetrabenazine has been shown to improve gating of abnormal visual stimuli and improve postural stability in Huntington disease (HD) patients as measured by computerized dynamic posturography testing. This study aims to elucidate whether partial dopaminergic depletion via low dose tetrabenazine has a similar effect on masking out of abnormal visual stimuli on the Stroop interference test.

Detailed description:

Arms: arm 1: Tetrabenazine will be withdrawn for at least 3 days in Huntington disease patients currently taking the medication.
Interventions: intervention 1: Tetrabenazine withdrawal
Intervention descriptions: intervention 1: Tetrabenazine will be withdrawn for at least 3 days in Huntington disease patients currently on the drug. Patients will be examined via Stroop test in the OFF state. Two doses of 12.5 mg tetrabenazine will be introduced, spaced 3 hours apart. Stroop test will be performed 6 hours after initial OFF Stroop test.

Protocol documents:
Prot_SAP_000.pdf: 
  
  
  
  
  
        
      
Official Title: Effect of tetrabenazine on Stroop 
interference in Huntington disease  
 
NCT: NCT0183491 
ID: L-10,830 
Document Date: 5/25/2016 
 
 
 


Effect of tetrabenazine on Stroop interference in 
Huntington disease 
  
Robert Fekete, M.D.  
  
 
Protocol, Statistical Analysis Plan, and Results 
 
 
  
 
 


 
  
  
Specific Aim  
  
Tetrabenazine has been shown to improve gating of abnormal visual stimuli and improve 
postural stability in Huntington disease (HD) patients as measured by computerized dynamic 
posturography testing [1]. This study aims to elucidate whether partial dopaminergic 
depletion via low dose tetrabenazine has a similar effect on masking out of abnormal visual 
stimuli on the Stroop interference test.  
  
Background  
  
The effect of tetrabenazine on chorea has been well established [2], Additional effects which 
may not necessarily involve chorea and may involve improvement in information processing 
of divergent stimuli have only recently been elucidated [1].   
  
This study investigates whether partial dopaminergic depletion via brief administration of 
low dose tetrabenazine has a beneficial effect on Stroop scores in Huntington disease 
patients. Showing an improvement in processing of visual stimuli at a lower dose chorea 
would be an intriguing possibility, further supporting a separate, chorea-independent 
mechanism for some of tetrabenazine’s beneficial effects. Most likely, this is a dopamine 
related effect involving information processing in the frontal lobe [1]. Dopaminergic blockade 
in healthy volunteers with haloperidol has been shown to reduce Stroop interference [3].  
Dietary dopaminergic depletion in healthy volunteers also reduced Stroop interference [4].   
  
The study is aimed as a pilot study. If results are promising, a larger trial with longer-term 
administration of tetrabenazine and more frequent, blinded measurements of Stroop 
interference during the titration period may be considered.   
  
Analysis of raw scores from Stroop testing in the Huntington Study Group trial [2] showed a 
statistically significant decline in the raw word reading score, but no significant changes in 
the raw color reading or raw interference scores. Calculated Stroop scores using either the 
Golden or Chafetz formulae [5] were not reported for this trial. It may be possible that the 
Chafetz score would properly account for slower word reading in tetrabenazine treated 
Huntington disease patients and show reduction in interference even if the raw interference 
score remains unchanged. For this reason, raw as well as calculated interference scores via 
both formulae will be reported in this trial. A three day withdrawal of steady state high 
tetrabenazine by Fekete et al. showed a significant effect on the calculated Stroop test [5].  
  
Methods:  
  
Study design:  
Ten subjects who are residents of Terence Cardinal Cooke (TCC) nursing home and have an 
established diagnosis of Huntington disease will be recruited by the principal investigator for 
participation in this study. Anticipated breakdown subject numbers by sex or ethnic 
categories is not known.   
  


Key inclusion criteria for the study will be:  
1. Established diagnosis of Huntington disease by movement disorders expert  
2. Patients not currently taking tetrabenazine as well as those off tetrabenazine for at least 
three days will be enrolled  
3. Patients should not have taken dopamine receptor blocking medication for at least three 
days (as this has been shown to affect the Stroop score in normals [3]).  
  
The data collection instrument is the standard Stroop color naming, word reading, and 
interference test.  
  
Stroop test will be administered to patients in the morning to patients who are OFF 
tetrabenazine (de novo or three day withdrawal). 12.5 mg of TBZ will be administered just 
after the first Stroop test and also 3 hours later. ON Stroop test will be administered 6 hours 
after the OFF Stroop test.  
The raw word reading, color reading, and interference scores will be recorded and used for 
further analysis.   
  
Resources:  
The study will be conducted at Terence Cardinal Cooke (TCC) nursing home, which has a 
dedicated wing exclusively for HD patients. The staff members in the HD unit have years of 
experience in dealing with the challenges of HD care. In addition, they have years of 
experience of treating HD with tetrabenazine.  
  
Evaluation:  
Statistical analysis:  
The three raw Stroop scores will be compared between ON and OFF groups. In addition, both 
Golden and Chafetz interference scores will be calculated, with customary age correction 
according to established convention. The ON and OFF scores may be compared using paired 
Student’s t-test in the cases of raw scores and Golden calculated scores. Chafetz scores will be 
compared via Wilcoxon signed rank test.   
  
Power analysis  
Given that a study examining effect on Stroop scores in the setting of low dose tetrabenazine 
administration has not been previously performed, the size of the potential effect is not 
known and hence direct power analysis is not possible.   
  
The closest study from which to obtain effect size on Stroop test for power analysis is a three 
day withdrawal of steady state tetrabenazine [6]. Using Glass’s ó formula:  
  
d= | averagea- averageb | / stdevcontrol d= |14.3-7.72| / 7.5 = 0.8773 
alpha=0.05 for single tailed t test power=1-beta error=0.95 with sample size of 8 
as calculated by G Power software  
  
Safety monitoring:  


The principal investigator will always be reachable in case of side effects. If an untoward side 
effect such as worsening of depression does occur after the first dose, the patient will be 
withdrawn from the study. It is expected that frequency and severity side effects will be low 
given the low dose and brief period of administration of the study drug. It is important to note 
that the side effects listed in the prescribing information for tetrabenazine were noted during 
dose escalation towards higher target doses and are aggregates of side effects during multi-
week studies.  
  
References  
1. 
Fekete R, Davidson, A, Cohen HS, Ondo WG. Effects of tetrabenazine on computerized 
dynamic posturography in Huntington disease patients. Park Rel Dis  
Epub: May 2012 doi:10.1016/j.parkreldis.2012.04.029  
2. 
Huntington Study Group. Tetrabenazine as antichorea therapy in Huntington disease: 
a randomized controlled trial. Neurology 2006; 66: 366-72.  
3. 
Williams JH, Wellman NA, Geaney DP, et al. Haloperidol reduces Stroop interference 
and increases negative priming in healthy 314 people. Schizophr Res 1996; 18: 223.  
4. 
Scholes KE, Harrison BJ, O’Neill BV, et al. Acute serotonin and dopamine depletion 
improves attentional control: findings from the Stroop task. Neuropsychopharm 
2007; 32: 1600-10.  
5. 
Chafetz M, Matthews LH. A New Interference Score for the Stroop Test. Arch Clin 
Neuropsychol 2004; 19: 555-67.  
6. 
Fekete R, Davidson A, Jankovic J. Clinical assessment of the effect of tetrabenazine on 
functional scales in Huntington disease: a pilot open label study. Tremor Other  
Hyperkinet Mov 2012;2: http://tremorjournal.org/article/view/86  
 
Results 
Only two patients were enrolled in the study. Their results are not amenable to statistical 
analysis given low enrollment.