Cognitive Effects of Vinpocetine in Healthy Adults and Patients With Epilepsy

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.

Study Overview

• Status: Suspended
• Conditions: Epilepsy
• Intervention / Treatment: Drug: Vinpocetine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Stanford University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria - Healthy (enrollment of healthy volunteers has been completed)

1. Healthy adults 18-60 years old
2. Proficient English
3. 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

1. Adults (18-60 years old) with localization related epilepsy
2. 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.
3. Proficient English
4. Patient complains of memory problems.
5. Neurological Disorders Depression Index -Epilepsy (NDDI-E) score <16
6. Mini-Mental Status Exam (MMSE) score <22
7. No history of status epilepticus in last year
8. No prior epilepsy surgeries
9. 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.
10. 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:

1. Major medical disease (e.g., epilepsy, diabetes, heart disease, active cancer, depression)
2. 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.
3. Use of centrally active medications
4. History of allergy to vinpocetine
5. Scores onintelligence quotient (IQ) <80 or Medical College of Georgia (MCG) Paragraph score < 2 standard deviations below norm.
6. Pregnancy or lactation.

Exclusion Criteria- Epilepsy

1. Major medical disease (e.g., diabetes, heart disease, active cancer, depression)
2. Use of centrally active medications
3. History of allergy to vinpocetine
4. Progressive Cerebral Disease (e.g., Alzheimer's disease)
5. Aphasia
6. Taking more than 3 AEDs
7. Pregnancy or lactation
8. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Low dose; Vinpocetine 10 mg Healthy subjects	Drug: Vinpocetine; 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; Other Names: ethyl apovincaminate; ethyl apovincaminoate; eburnamenine-14-carboxylic acid ethyl ester; 3 alpha, 16 alpha-apovincaminic acid ethyl ester; ethyl apovincamin-22-oate; Cavinton®; Ceractin; ARGH-4405
Active Comparator: Mid-dose 1; Vinpocetine 20mg Healthy subjects	Drug: Vinpocetine; 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; Other Names: ethyl apovincaminate; ethyl apovincaminoate; eburnamenine-14-carboxylic acid ethyl ester; 3 alpha, 16 alpha-apovincaminic acid ethyl ester; ethyl apovincamin-22-oate; Cavinton®; Ceractin; ARGH-4405
Placebo Comparator: Placebo; 0 dose of vinpocetine Healthy and Epilepsy subjects	Drug: Vinpocetine; 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; Other Names: ethyl apovincaminate; ethyl apovincaminoate; eburnamenine-14-carboxylic acid ethyl ester; 3 alpha, 16 alpha-apovincaminic acid ethyl ester; ethyl apovincamin-22-oate; Cavinton®; Ceractin; ARGH-4405
Active Comparator: High Dose; Vinpocetine 60 mg single dose Healthy Subjects & 20mg tid Epilepsy Subjects	Drug: Vinpocetine; 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; Other Names: ethyl apovincaminate; ethyl apovincaminoate; eburnamenine-14-carboxylic acid ethyl ester; 3 alpha, 16 alpha-apovincaminic acid ethyl ester; ethyl apovincamin-22-oate; Cavinton®; Ceractin; ARGH-4405

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Stanford University
• Investigators: Principal Investigator: Kimford J Meador, MD, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2012
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: December 4, 2013
• First Submitted That Met QC Criteria: December 10, 2013
• First Posted (Estimated): December 16, 2013

Study Record Updates

• Last Update Posted (Actual): July 12, 2023
• Last Update Submitted That Met QC Criteria: July 10, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: memory; epilepsy; cognition
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Neuroprotective Agents; Protective Agents; Phosphodiesterase Inhibitors; Nootropic Agents; Vinpocetine
• Other Study ID Numbers: IRB00044949; Stanford Vinpocetine (Other Identifier: Other)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No