BackgroundQuantitative digital assessments in clinical trials may increase effect sizes while reducing population sizes, resulting in more accurate and cost effective trials and less burden for ...participants, compared to qualitative scales. In an internship program (University of Tübingen - TüREx), we explored the feasibility of dual-task assessments using the Q-Motor devices, to amplify differentiation between HD gene carriers and healthy controls.AimsTo assess feasibility of a dual-task design of Q-Motor finger tapping and target pointing task in a small cohort.Methods10 healthy controls (non-gene carriers or status unknown) and 5 manifest and pre-manifest HD gene carriers have been enrolled in this proof-of-concept project. Participants were asked to perform three Q-Motor tasks: 1) Speeded finger tapping (non-dominant hand); 2) 3D pointing with the position tracking Polhemus Stylus to defined targets on a x-y plane installed in front of the subject in a pre-defined sequence (dominant hand); 3) Interference task, performing both tasks simultaneously.ResultsWe found that while neither task single performed task could differentiate between the participant groups, the interference task showed good differentiation (p < 0.01) between the groups for defined parameters. Specifically, HD gene carriers tended to use higher tapping forces in finger tapping, when doing target pointing simultaneously.ConclusionsWe found assessment of the described dual-tasks using Q-Motor devices feasible and well tolerated. While we acknowledge the limitations of the small sample size and unmatched groups, the results are encouraging and support confirmation of these findings in a larger cohort longitudinal study.
BackgroundQ-Motor provided reliable quantitative endpoints in TRACK-HD and several clinical trials. Finger tapping was the most sensitive assessment of disease progression and to detect treatment ...effects. Recently a foot tapping test was introduced to expand Q-Motor to the lower extremity. However, subjects had difficulties to properly lift the foot from the force sensor.AimsTo assess the feasibility of using a novel foot tapping apparatus that requires subjects to lift their foot properly.MethodsTwo novel setups were constructed with the force sensor above the foot, one using a rigid (G1), one with a non-rigid bar (G2) to carry the sensor. Both setups were compared with the old setup carrying the sensor underneath the foot (G3). 6 healthy controls were asked to perform the foot tapping task on each setup on 4 consecutive days. They tapped with the foot on the force sensor as fast as possible for 10 seconds with 5 repetitions at each foot.ResultsThe ‘Tap-Speed-Inter-Onset-Interval-Mean-Foot’ is the main endpoint of foot tapping. It is the average time between the start of each successive tap. A density plot showed normally distributed data only for G2 and G3, thus G1 was not analyzed further. The data showed that the new inverted test setup (G2) provided less variability and better reproducibility over time.ConclusionsThe novel foot tapping task is feasible and provided more reliable data. The new setup with the non-rigid bar merits further exploration in upcoming studies and should be tested in a larger cohort of subjects over longer periods.
BackgroundQ-Motor assessments have been used in a number of large multicenter clinical studies in Huntington’s disease and beyond. Q-Motor has proven to be a robust and sensitive tool to track and ...compare motor performance cross-sectionally or longitudinally, reducing placebo effects and rater bias compared to clinical scales.AimsThe current study investigated whether the application of Q-Motor assessments in a large population-based sample is feasible, and whether it provides the opportunity to generate normative data and to investigate the effects of demographic variables on Q-Motor measures.MethodsThe BiDirect study is an observational, prospective cohort study conducted at the University of Muenster in Germany. All participants, including the population-based control cohort, performed the Q-Motor speeded tapping (digitomotography) and grasping & lifting (manumotography and choreomotography) tasks. Normative data was gathered with regard to age and sex, thereby considering further mediating variables. Effects were estimated using univariate multiple linear regression analyses.ResultsThe use of Q-Motor assessments was feasible in the setting of this longitudinal cohort study. Normative data was generated for all tasks applied and measures proposed. The applied models showed significant effects of age and sex on some tapping speed measures and involuntary movements: participants showed decreasing performance with increasing age. Moreover, women tended to tap slower than men, and the non-dominant hand showed reduced performance compared to the dominant hand across tests.ConclusionsQ-Motor assessments are feasible for population-based cohort studies. The normative data generated here will enable comparative analysis in other studies and clinical trials, including more robust conclusions about clinical change.
BackgroundLarge animal models, such as the transgenic (tg) Huntington disease (HD) minipig, have been proposed to improve translational reliability and assessment of safety, efficacy and tolerability ...in preclinical studies. Minipigs are characterised by high genetic homology and comparable brain structures to humans. In addition, behavioural assessments successfully applied in humans could be explored in minipigs to establish similar endpoints in preclinical and clinical studies. The tongue protrusion assessment (glossomotography) was successfully established as part of the Q-Motor system and showed correlated to UHDRS-TMS motor dysfunction and changes in brain imaging in premanifest and manifest HD. Recently, a tongue test was also established to assess minipig motor performance.AimThe aim of this project was to further develop the minipig tongue test to incorporate quantitative measurements. The tgHD minipigs do not show any overt changes in their behavior, thus sensitive assessment of minor changes detectable compared to wildtype (wt) minipigs would be useful.MethodsThe existing tongue board has been modified to use it with only one hole. At the bottom of the hole a force sensor was mounted connected to an Arduino Uno R3 to readout the sensor and a Raspberry Pi 3B to log the recorded data. To be able to expose animals to variable degrees of motor challenge, the hole depths was adjustable in depth. To motivate the minipigs to touch the sensor with their tongue the hole was filled with soaked feed pellets as reward.ResultsThe tongue protrusion force was measured in three different levels of depths. Reliable and well reproducible assessment was feasible, but were no differences between wt and tgHD minipigs were detected at the age investigated.ConclusionThe developed tongue board is able to measure quantitative tongue protrusion forces. The next step is to explore whether minipigs can be trained to actively press their tongue against the sensor to obtain a pre-defined reward.AcknowledgementThis study was funded by donations of HD families.
BackgroundClinical rating scales in clinical trials for Huntington’s disease (HD) have shown limited sensitivity in the premanifest stage of HD and often suffer from inter- and intra-rater ...variability and bias. Thus, there is an unmet need for objective and reliable assessments to serve as outcome measures in clinical trials. The Q-Motor, a sensor-based assessment battery, was developed to provide accurate and precise quantification of motor performance. During the analysis of the TRACK-HD study, a couple of variables turned out to be particularly sensitive, but further approaches on testing alternative variables have not been conducted, yet.ObjectiveTo identify novel conceptual variables for the Q-Motor digitomotography (speeded tapping) assessment, that have the potential to be more sensitive and robust particularly in the premanifest stage. The applicability of these variables should be investigated for cross-sectional and longitudinal analyses, using the TRACK-HD data.MethodsQ-Motor raw-data from the TRACK-HD study was used to extract the novel variables. The data sample included 4 year follow up data from 288 participants (age: 48 ± 10 years, female: 124, number of unaffected controls: 94). Statistical analyses were conducted using R. Generalized linear mixed models and ANOVA was used for group comparisons cross-sectional and longitudinally. Correlation with clinical rating scales and imaging parameters was performed.ResultsMost novel identified variables allow discrimination between controls pre-HD and manifest HD groups. Some even show significance in the more subtle distinction between pre-HD subgroups. Most variables also show good correlations with the clinical Total Motor Score (TMS) and with several magnet resonance (MR) imaging variables.ConclusionThe sensitivity observed in the novel variables is comparable to that of previously used variables. However, the additional information may be useful for the creation of a combined measure, which will be explored in a next step.
To increase the reliability of translating preclinical findings to humans, large animal models, such as the transgenic (tg) Libechov minipig, were established. As minipigs possess high genetic ...homology with humans and have similarities in anatomy, physiology and metabolism to humans, they are considered for studying neurodegenerative diseases longitudinally. Recently, sleep abnormalities and changes in circadian rhythm in Huntington's disease (HD) patients were acknowledged to present one of the early symptoms in HD.
The aim of the present study was to explore the activity behaviour of Libechov minipigs and to investigate whether tgHD and wildtype (wt) minipigs exhibit differences in activity behaviour. Furthermore, it was investigated whether activity assessments may serve as reliable endpoints for phenotyping minipigs transgenic for the Huntington gene.
Activity behaviour of minipigs was studied by video recording the stables twice a week over a total study period of five weeks for a cohort of five tgHD minipigs and five wt minipigs. Statistical analysis was performed using the linear mixed model. Once a week, the distances covered by two minipigs in focus (tgHD, wt) were measured using the VideoMotionTracker® software.
Libechov minipigs showed a biphasic pattern of activity, spending most of the time inactive or grubbing in litter. Differences in activity behaviour (rooting, resting and standing) were detected between wt and tgHD minipigs. The influence of the genotype on behavioural patterns was observed during circadian monitoring. TgHD minipigs covered longer distances on average and during every 24 h observation period than wt minipigs.
Activity behaviour may be a viable marker for phenotyping minipigs transgenic for the Huntington gene. Video recordings of behavioural patterns provide a non-invasive opportunity to capture potential disease signs. Phenotypic progression including the age of disease manifestation may be explored by documentation of circadian characteristics.
