Cognitive Effects of Vinpocetine in Healthy Adults and Patients With Epilepsy

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.

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.