Category: MSA, PSP, CBS: Clinical Trials
Objective: The NORAPS phase II study (ISRCTN99462035) investigates the safety, tolerability and efficacy of atomoxetine in Progressive Supranuclear Palsy (PSP).
Background: PSP is a neurodegenerative disease with limited treatment options. Neuropsychiatric symptoms, including apathy and impulsivity, are common. Post-mortem data show early and severe noradrenergic cell loss in the locus coeruleus, which is associated with apathy and impulsivity. Atomoxetine, a noradrenaline reuptake inhibitor, has shown efficacy against markers of apathy and impulsivity in experimental studies of PSP and Parkinson’s disease.
Method:
Patients with probable or possible PSP undergo screening before a double-blinded randomised crossover study, with two 8-weeks periods with 40mg atomoxetine or matched placebo. Exclusion criteria include cardiac arrhythmias, ischaemic heart disease and concurrent noradrenergic treatments. Participants are invited to baseline MRI scan, with MT-weighted imaging for locus coeruleus integrity at 3T or 7T. Co-primary outcomes are safety and efficacy on the Cambridge Behavioural Inventory’s challenging-behaviours subscale. Secondary and exploratory outcome measures include the PSP rating scale, response-inhibition paradigm, CGI, HADS, CAARS, CBI-R, RBANS, MOCA, FAB, PSP-QoL and the effects of baseline locus coeruleus variance on drug response.
Results:
As of submission, 74 patients have been recruited across six sites. Target enrolment is 84 participants, to achieve 80% power for primary endpoints with 10% attrition. Recruitment will end in April 2025. Preliminary analysis of baseline recruitment data confirms that the challenging behaviours subscale of the Cambridge Behavioural Inventory correlates with impulsivity (FAB), depression and anxiety (HADS) and carer quality of life. Meanwhile, disease severity (PSPRS) correlates with restlessness, apathy, impulsivity (CAMQUAIT, Conner’s), worse cognition (RBANS, MOCA) and lower patient quality of life.
Conclusion:
NORAPS tests the hypothesis that atomoxetine is safe and well tolerated in PSP, with benefits on apathy and impulsivity. A secondary hypothesis to be tested is that behavioural and cognitive outcomes are dependent on baseline integrity of the locus coeruleus noradrenergic system. Given locus coeruleus involvement in various neurodegenerative disorders, findings from NORAPS may have broad transdiagnostic implications.
To cite this abstract in AMA style:
R. Durcan, H. Paula, D. Street, A. Murley, S. Jones, A. Church, C. Kobylecki, V. Marshall, C. Antoniades, B. Ghosh, J. Rowe. Noradrenaline treatment of apathy and impulsivity in participants with Progressive Supranuclear Palsy syndromes (NORAPS) [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/noradrenaline-treatment-of-apathy-and-impulsivity-in-participants-with-progressive-supranuclear-palsy-syndromes-noraps/. Accessed October 5, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/noradrenaline-treatment-of-apathy-and-impulsivity-in-participants-with-progressive-supranuclear-palsy-syndromes-noraps/