Cognitive Effects of Vinpocetine in Healthy Adults and Patients With Epilepsy

Study Overview
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Brief Summary
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Pilot studies in healthy volunteers and in patients with epilepsy to assess the potential efficacy and safety of different dosages of vinpocetine in improving cognition.

Detailed Description
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Cognitive problems are common in patients with epilepsy, but there is currently no specific treatment available. Vinpocetine is a chemical obtained from the leaves of the Lesser Periwinkle. It has been shown to improve cerebral metabolism and memory in animals and humans. In addition, it has been shown to enhance long-term potentiation, which has been linked to memory mechanisms. Furthermore, vinpocetine has been shown to have anticonvulsant effects and is more potent than several commonly used antiepileptic drugs (i.e., carbamazepine, phenytoin, valproate, oxcarbazepine, lamotrigine and topiramate) in inhibiting both sodium and calcium channels, which control release of excitatory neurotransmitters that can lead to brain injury. Thus, vinpocetine might offer a unique drug to help cognition in patients with epilepsy. The investigators propose to conduct pilot studies in healthy volunteers and in patients with epilepsy to assess the potential efficacy and safety of different dosages of vinpocetine in improving cognition. Specific Aim 1a: To determine if vinpocetine enhances memory and other cognitive functions in healthy volunteers. Specific Aim 1b: To determine blood levels from 3 different acute oral doses of vinpocetine in healthy volunteers. Specific Aim 2a: To provide safety and preliminary of efficacy data that vinpocetine can enhance memory and other cognitive functions in patients with epilepsy. Specific Aim 2b: To determine blood levels from acute and chronic oral doses of vinpocetine in patients with epilepsy as well as effects on anticonvulsant blood levels. Specific Aim 2c: To provide preliminary of data that vinpocetine can reduce seizure frequency or duration in patients with epilepsy.

Official Title
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Cognitive Effects of Vinpocetine in Healthy Adults and Patients With Epilepsy

Conditions
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Epilepsy

Intervention / Treatment
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* Drug: Vinpocetine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria - Healthy (enrollment of healthy volunteers has been completed) Healthy adults 18-60 years old Proficient English Use of appropriate contraception if woman of childbearing potential. This must include complete abstinence for the duration of the study or use of a barrier method plus one other contraceptive method (e.g. hormonal contraception or intrauterine device, IUD). Inclusion Criteria -Epilepsy Adults (18-60 years old) with localization related epilepsy Patient is on stable antiepileptic drug therapy for last 2 months and is willing to remain on same therapy for the duration of the study. Proficient English Patient complains of memory problems. Neurological Disorders Depression Index -Epilepsy (NDDI-E) score <16 Mini-Mental Status Exam (MMSE) score <22 No history of status epilepticus in last year No prior epilepsy surgeries Stable antiepileptic drug (AED) therapy for last 2 months or more and willing not to change for 2 months. Vinpocetine will be stopped and the patient will be withdrawn from the study if marked changes occur in seizures or if other adverse events occur. Use of appropriate contraception if woman of childbearing potential. This must include complete abstinence for the duration of the study or use of a barrier method plus one other contraceptive method (e.g. hormonal contraception or IUD). Exclusion Criteria -Healthy: Major medical disease (e.g., epilepsy, diabetes, heart disease, active cancer, depression) Subject has a lifetime history of suicide attempt (including an active attempt, interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6 months as indicated by a positive response ('Yes') to either Question 4 or Question 5 of the Columbia Suicide Severity Rating Scale (C-SSRS) at Screening. Use of centrally active medications History of allergy to vinpocetine Scores onintelligence quotient (IQ) <80 or Medical College of Georgia (MCG) Paragraph score < 2 standard deviations below norm. Pregnancy or lactation. Exclusion Criteria- Epilepsy Major medical disease (e.g., diabetes, heart disease, active cancer, depression) Use of centrally active medications History of allergy to vinpocetine Progressive Cerebral Disease (e.g., Alzheimer's disease) Aphasia Taking more than 3 AEDs Pregnancy or lactation Subject has a lifetime history of suicide attempt (including an active attempt, interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6 months as indicated by a positive response ('Yes') to either Question 4 or Question 5 of the C-SSRS at Screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Double-blind single dose crossover with 1-month follow-up open label in patients.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Low dose<br>Vinpocetine 10 mg Healthy subjects | Drug: Vinpocetine<br>* Vinpocetine is a chemical obtained from the leaves of the Lesser Periwinkle. It has been shown to improve cerebral metabolism and memory in animals and humans. In addition, it has been shown to enhance long-term potentiation, which has been linked to memory mechanisms. Furthermore, vinpocetine has been shown to have anticonvulsant effects and is more potent than several commonly used antiepileptic drug<br>* Other names: ARGH-4405;|
| Active Comparator: Mid-dose 1<br>Vinpocetine 20mg Healthy subjects | Drug: Vinpocetine<br>* Vinpocetine is a chemical obtained from the leaves of the Lesser Periwinkle. It has been shown to improve cerebral metabolism and memory in animals and humans. In addition, it has been shown to enhance long-term potentiation, which has been linked to memory mechanisms. Furthermore, vinpocetine has been shown to have anticonvulsant effects and is more potent than several commonly used antiepileptic drug<br>* Other names: ARGH-4405;|
| Placebo Comparator: Placebo<br>0 dose of vinpocetine Healthy and Epilepsy subjects | Drug: Vinpocetine<br>* Vinpocetine is a chemical obtained from the leaves of the Lesser Periwinkle. It has been shown to improve cerebral metabolism and memory in animals and humans. In addition, it has been shown to enhance long-term potentiation, which has been linked to memory mechanisms. Furthermore, vinpocetine has been shown to have anticonvulsant effects and is more potent than several commonly used antiepileptic drug<br>* Other names: ARGH-4405;|
| Active Comparator: High Dose<br>Vinpocetine 60 mg single dose Healthy Subjects & 20mg tid Epilepsy Subjects | Drug: Vinpocetine<br>* Vinpocetine is a chemical obtained from the leaves of the Lesser Periwinkle. It has been shown to improve cerebral metabolism and memory in animals and humans. In addition, it has been shown to enhance long-term potentiation, which has been linked to memory mechanisms. Furthermore, vinpocetine has been shown to have anticonvulsant effects and is more potent than several commonly used antiepileptic drug<br>* Other names: ARGH-4405;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in CNS Vitals Composite Score | CNS Vitals consists of multiple subtasks that provide an overall composite score will be the primary outcome measure | Healthy - weekly treatment visits 1-4; Epilepsy =treatment weeks 4, 8, & 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | safety outcome | Healthy - weekly treatment visits 1-4; Epilepsy =treatment weeks 4, 8, & 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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epilepsy, cognition, memory