Nerinetide showed no significant association with brain volume changes in stroke patients receiving endovascular therapy.
Photo by Ben Maffin / Unsplash
Key Takeaway
Note that this small sub-study found no significant association between nerinetide and brain volume changes in EVT-treated stroke patients.
This prospective, multisite MRI sub-study of the ESCAPE-NA1 trial evaluated 43 patients receiving endovascular therapy (EVT) for stroke. The investigation compared nerinetide against placebo to assess changes in brain structure and function over a 90-day follow-up period. The primary outcome measured the change in whole-brain volume between day 1 and day 90, while secondary outcomes included ventricular enlargement, cortical grey matter volume loss, subcortical white matter volume loss, thalamic volume loss, hippocampal volume loss, and functional outcome at 90 days.
Analysis of the primary outcome revealed significant whole-brain volume loss (P < .001) and significant ventricular enlargement (P < .001) within the study population. Significant losses were also observed in cortical grey matter (P = .001), subcortical white matter (P < .001), thalamic volume (P < .001), and hippocampal volume (P < .001). However, the study found no significant association between nerinetide treatment and these volume changes. Additionally, predictors of functional independence were identified with P-values of < .001, though specific effect sizes or absolute numbers for these outcomes were not reported.
Safety and tolerability data, including adverse events, serious adverse events, discontinuations, and specific tolerability metrics, were not reported in the study. Key limitations include the small sample size of 43 patients, the lack of absolute numbers for volume changes, and the absence of reported safety information. As this was a sub-study, the results may not be generalizable to broader stroke populations. Consequently, the clinical relevance of nerinetide for preventing brain volume loss in this setting remains unclear.
More on Stroke
Chiglitazar reduces liver fat in MASLD patients with hypertriglyceridemia and insulin resistance
Two doses of chiglitazar cut liver fat far more than a placebo in 18 weeks
In a phase II randomized, double-blind, placebo-controlled trial, 104 patients with MASLD, hypertriglyceridemia, and insulin resistance rece…
Patients with fatty liver disease and high triglycerides saw liver fat drop significantly with chiglitazar compared to placebo after 18 week…
Oral Sodium Butyrate Reduces Weight in Overweight Adults Without Diabetes
Oral sodium butyrate helps overweight adults without diabetes lose weight
This 12-week proof-of-concept RCT in 46 overweight adults (23 with type 2 diabetes) found that oral sodium butyrate 1875 mg/day led to great…
A new trial shows oral sodium butyrate helps adults without diabetes lose more weight than a placebo over three months.
Essential phospholipids reduced hepatic steatosis and improved HbA1c in patients with MASLD and type 2 diabetes over 6 months.
Essential Phospholipids Reduce Liver Fat In Six Months
This randomised, placebo-controlled phase 4 trial enrolled 193 patients with metabolic dysfunction-associated steatotic liver disease and ty…
Essential phospholipids may lower liver fat and improve energy levels for people with fatty liver disease and diabetes within just six month…
Exoskeleton-assisted robotic therapy improves upper limb motor scores versus conventional rehabilitation in poststroke inpatients
Robotic Therapy Helps Stroke Patients Regain Arm Function Faster
This multicenter, single-blind randomized controlled trial enrolled 94 inpatients with moderate-to-severe upper limb impairment within three…
A trial of 94 stroke patients found robotic arm therapy led to significantly better motor recovery than standard rehabilitation within five …
View Original Abstract ↓
BACKGROUND: Brain injury due to stroke is an important determinant of long-term disability. The acute lesion visible on MRI with DWI underestimates the total burden of the ischaemic injury. The objectives of this study are: (1) quantify the delayed secondary ischaemic injury volume by calculating the whole and regional brain volume loss at 90-days post-stroke and (2) determine whether brain volume loss independently predicted functional outcome at 90 days.
METHODS: REPERFUSE-NA1 is a prospective, multisite MRI sub-study of the ESCAPE-NA1 trial (ClinicalTrialGov #NCT02930018), which randomised participants receiving endovascular therapy (EVT) to nerinetide versus placebo. MRI was acquired immediately after therapy (day 1, <5 hours post-EVT) and at 90-days. The primary outcome was change in whole-brain volume between day 1 and 90. Serial MR metrics were used to generate sample size calculations for future neuroprotectant trials.
RESULTS: A total of 43 patients of mean age 65.1 years (SD = 14.9, 51.2% female, median NIHSS 15 [Q1-Q3 = 11-20]) were included. In the entire cohort, there was significant whole-brain volume loss (P < .001), ventricular enlargement (P < .001), and cortical grey matter (P = .001), subcortical white matter (P < .001), thalamic (P < .001), and hippocampal (P < .001) volume loss in the ipsilateral hemisphere. Baseline DWI volume and ipsilateral hemispheric brain atrophy were significant predictors of functional independence, with P-values of < .001. There was no significant association between nerinetide treatment and volume changes at 90-days. For a prospective 90-day neuroprotectant trial to demonstrate 50% reduction, 41 patients per group would be needed using ventricular volume change.
CONCLUSION: This study indicates that whole-brain volume loss is a feasible measurement of delayed secondary ischaemic injury. Future neuroprotectant clinical trials could utilise MR-based markers of delayed ischaemic injury.
Intravenous tenecteplase improves functional outcomes but increases hemorrhage risk in non-large vessel occlusion acute ischemic stroke.
Tenecteplase improves stroke recovery but increases bleeding risk in late treatment window
Related in Neurology
Aerobic and strength training reduce fatigue in multiple sclerosis patients
Aerobic or strength training eases MS fatigue, trial finds
This randomized effectiveness trial in 62 persons with multiple sclerosis and fatigue found that 8 weeks of aerobic training, strength train…
A small trial finds that aerobic and strength training each reduce fatigue in MS, with no clear winner among exercise types.
Modified CIMT with trunk restraint improves function in chronic stroke patients
Six weeks of tailored therapy improved function and quality of life for chronic stroke patients.
A single-blinded RCT in 34 chronic stroke patients found that adding patient-tailored modified constraint-induced movement therapy (mCIMT) w…
Thirty-four people with long-term stroke saw better movement and balance after six weeks of a specific therapy mix compared to standard care…
Laughter yoga reduced fatigue in people with multiple sclerosis in a randomized controlled trial
Laughter Yoga Cuts Fatigue And Improves Sleep For Multiple Sclerosis Patients
This randomized controlled trial enrolled 42 people with multiple sclerosis. Participants in the intervention group received 12 sessions of …
People with multiple sclerosis who practiced laughter yoga reported less tiredness and better sleep after just twelve sessions.
Exercise training improves cognition and fatigue in older adults with multiple sclerosis
Exercise boosts brain and cuts fatigue in older adults with MS
This Phase-Ib randomized controlled trial in 51 older adults with multiple sclerosis found that 16 weeks of home-based aerobic and resistanc…
A 16-week home exercise program improved thinking speed, executive function, fatigue, and quality of life in older adults with multiple scle…
From Other Specialties
Vitamin D supplementation may reduce disease activity in SLE: a systematic review and meta-analysis
Vitamin D supplements may calm lupus activity, study finds
This systematic review and meta-analysis of 847 patients with systemic lupus erythematosus found that vitamin D supplementation significantl…
A new analysis of 847 lupus patients suggests vitamin D supplements may reduce disease activity and improve immune markers.
Observational study assesses MiniDock MTB diagnostic accuracy against Xpert in Indonesian TB patients
New TB test shows promise in Indonesia trial
This observational study evaluated the diagnostic accuracy of MiniDock MTB on sputum swabs compared to Xpert MTB/RIF Ultra and liquid cultur…
A new TB test called MiniDock MTB accurately detected TB in adults, but sensitivity dropped in children and low-burden cases.
Phase 1 study traces ainuovirine metabolism and excretion in healthy men
A single dose of oral ainuovirine clears the body within two days in healthy men
This phase 1 open-label study in 6 healthy men examined the pharmacokinetics and mass balance of a single dose of radiolabelled ainuovirine.…
A single dose of oral ainuovirine clears the body within two days in healthy men, with most of the drug leaving unchanged through urine and …
Nirmatrelvir/Ritonavir in Breast Milk: Low Infant Exposure in Lactating Women
Paxlovid levels low in breast milk, early study finds
This Phase 1 open-label study in 8 healthy lactating women found that nirmatrelvir/ritonavir concentrations in breast milk were consistently…
A small study finds that nirmatrelvir/ritonavir (Paxlovid) passes into breast milk at low levels, suggesting minimal infant exposure.