Verbatim patient-reported outcomes and trails making test B (TMT-B) performance in the REACH2HD trial
J.L. Purks, A. Zeymo, N.M. Shara, K.E. Anderson, I. Shoulson (Washington, DC, USA)
Meeting: 20th International Congress
Abstract Number: 1118
Keywords: Chorea (also see specific diagnoses,
Cognitive dysfunction,
etc): Treatment,
Huntingtons disease,
Memory disorders
Session Information
Date: Wednesday, June 22, 2016
Session Title: Huntington's disease
Session Time: 12:00pm-1:30pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: Examine the relationship between Trails Making Test B (TMT-B) performance and bothersome cognitive complaints among Huntington Disease (HD) research participants in the REACH2HD randomized-controlled trial of PBT2.
Background: The Phase-2 REACH2HD trial examined safety and benefits of the metals modulator PBT2 on cognitive impairment and found improvement on TMT-B, a validated measure of executive cognitive performance. The Huntington Disease Patient-Reported Outcome of Problems (HD-PROP) captures verbatim subject reports of their most bothersome problems.
Methods: The TMT-B and HD-PROP were administered to the 109 REACH2HD participants at baseline (BL) and Week 26 (W26) of experimental treatment (randomly assigned to PBT2 250 mg/day (n=36), PBT2 100 mg/day (n=38), or placebo (n=35)). Verbatim HD-PROP problems were categorized independently without knowledge of treatment assignment into seven umbrella terms. Change Scores of ‘Thinking Problems’ (CSTP) between BL – W26 were calculated for subjects who showed the greatest TMT-B improvement, subjects who showed the greatest TMT-B worsening, and subjects who had no change in TMT-B.
Results: Of the 15 subjects who exhibited the greatest improvement in TMT-B, the two who reported improvement in CTSP were both assigned to PBT2 250 mg/day (Zero CSTP = 9, Negative CSTP = 4). Of the 15 who exhibited the greatest worsening in TMT-B, four had favorable CSTP: 3 PBT2 250 and 1 PBT2 100 (Zero CSTP = 10, Negative CSTP = 0). Of the 17 subjects who had no change in TMT-B, four had favorable CSTP: 1 PBT2 250, 2 PBT2 100 and 1 placebo (Zero CSTP = 12, Negative CSTP = 1).
Conclusions: Within positive, negative, and no change TMT-B performance groups, 90% of improvement in CSTP occurred among PBT2-treated subjects, suggesting that the HD-PROP may capture the subjects’ own experience of meaningful improvement in cognition, observed in the REACH2HD trial on formal testing. Additionally, all positive CSTP reported zero W26 cognitive complaints, indicating absence of bothersome thinking problems. These results suggest that higher dosages of PBT2 may be associated with decreased thinking complaints reported in REACH2HD regardless of TMT-B performance. Further and wider implementation and pairing of patient, caregiver and clinician HD-PROP reports are essential to capture PROs and address cognition as an unmet need in HD.
(20min delay)