Efficacy of Souvenaid in Mild Alzheimer's Disease: Results from a Randomized, Controlled Trial

Abstract

Souvenaid aims to improve synapse formation and function. An earlier study in patients with Alzheimer's disease (AD) showed that Souvenaid increased memory performance after 12 weeks in drug-naïve patients with mild AD. The Souvenir II study was a 24-week, randomized, controlled, double-blind, parallel-group, multi-country trial to confirm and extend previous findings in drug-naïve patients with mild AD. Patients were randomized 1:1 to receive Souvenaid or an iso-caloric control product once daily for 24 weeks. The primary outcome was the memory function domain Z-score of the Neuropsychological Test Battery (NTB) over 24 weeks. Electroencephalography (EEG) measures served as secondary outcomes as marker for synaptic connectivity. Assessments were done at baseline, 12, and 24 weeks. The NTB memory domain Z-score was significantly increased in the active versus the control group over the 24-week intervention period (p = 0.023; Cohen's d = 0.21; 95% confidence interval [-0.06]-[0.49]). A trend for an effect was observed on the NTB total composite z-score (p = 0.053). EEG measures of functional connectivity in the delta band were significantly different between study groups during 24 weeks in favor of the active group. Compliance was very high (96.6% [control] and 97.1% [active]). No difference between study groups in the occurrence of (serious) adverse events. This study demonstrates that Souvenaid is well tolerated and improves memory performance in drug-naïve patients with mild AD. EEG outcomes suggest that Souvenaid has an effect on brain functional connectivity, supporting the underlying hypothesis of changed synaptic activity.

An exploratory clinical study of p38α kinase inhibition in Alzheimer's disease

“…In our clinical study, the ES that we saw for immediate and delay recall compares favorably to ES of ≤0.2 for WMS immediate or delayed recall at week 12 in the placebo‐treated subjects in two trials of Souvenaid in a similar patient population (mild AD, baseline MMSE = 24) 32, 33. Although with the absence of a placebo group our results could reflect practice effect, we think this is unlikely since the learning effects on episodic memory tests that are well recognized in cognitively intact older individuals are less prominent, or absent, in biomarker‐positive early AD 34, 35.…”

Targeting the Prodromal Stage of Alzheimer's Disease: Bioenergetic and Mitochondrial Opportunities

“…In a 24-week double-blind sex-balanced clinical trial with 259 patients aged 51-89 years (mean 74 years) with mild AD, Souvenaid significantly improved memory and synaptic connectivity measured by electroencephalography [193]. However, in a clinical trial with patients with moderate-to-severe AD, no significant improvement was associated with Souvenaid treatment [112,193], suggesting that the intervention window is early in AD progression.…”

“…A secondgeneration clioquinol molecule, PBT2, is in Phase II clinical trials (ClinicalTrials.gov identifier: NCT00471211). PBT2 [112,113,193] AD = Alzheimer's disease; NA, not available; Aβ = β-amyloid; EPA = eicospentaenoic acid; DHA = docosahexaenoic acid; EEG = electroencephalography reportedly decreased Aβ levels and improved performance on 2 cognitive function tests [191,192]. In addition to metal chelation, PBT2 has a second mechanistic action to increase Aβ clearance, increasing activity of matrix metalloproteases including neprilysin, insulin degrading enzyme, and tissue plasminogen activator [191,192].…”

“…The formulation also acts as a ketogenic dietary supplement with high fat content to provide ketone bodies to the brain. The formulation also contains antioxidants; vitamins A, C, E, riboflavin, and folic acid; selenium; and ions required for membrane potential balancing and mitochondrial function, including sodium, potassium, chloride, calcium, and zinc [193]. In a 24-week double-blind sex-balanced clinical trial with 259 patients aged 51-89 years (mean 74 years) with mild AD, Souvenaid significantly improved memory and synaptic connectivity measured by electroencephalography [193].…”

“…The formulation also contains antioxidants; vitamins A, C, E, riboflavin, and folic acid; selenium; and ions required for membrane potential balancing and mitochondrial function, including sodium, potassium, chloride, calcium, and zinc [193]. In a 24-week double-blind sex-balanced clinical trial with 259 patients aged 51-89 years (mean 74 years) with mild AD, Souvenaid significantly improved memory and synaptic connectivity measured by electroencephalography [193]. However, in a clinical trial with patients with moderate-to-severe AD, no significant improvement was associated with Souvenaid treatment [112,193], suggesting that the intervention window is early in AD progression.…”