Cognitive Impact of Pomegranate Polyphenols Following Ischemic Stroke

The Effects of Pomegranate Polyphenols on Neuropsychological Functioning Following Ischemic Stroke

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02442804

Enrollment

Registered

2015-05-13

Start date

2015-06-30

Completion date

2016-04-30

Last updated

2017-08-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Stroke

Keywords

Pomegranate, Stroke, Neuropsychology

Brief summary

The purpose of this study is to determine whether pomegranate supplements improve cognitive functioning following stroke.

Detailed description

Research suggests that antioxidants (substances that may slow or prevent cell damage) found in many fruits and vegetables may help improve brain functioning (for example, memory and attention) in healthy individuals and prevent cognitive decline in individuals who have suffered a stroke. The purpose of this research study is to examine whether dietary supplementation with an antioxidant extract can help promote healthy cognitive functioning as a component of recovery after stroke. The procedures include: Administering polyphenols via 2 POMx pills, each of which contains polyphenols derived from pomegranates equivalent to the content of approximately 8 ounces of pomegranate juice, or placebo pills (capsules containing no polyphenol ingredients), every day for one week to inpatients who are in the acute post-stroke phase. Neuropsychological testing pre- and post-treatment will determine whether cognitive functioning changes. Subjects will be randomized into either a placebo or polyphenol group.

Interventions

DIETARY_SUPPLEMENTPOMx

Pomegranate supplement (1g) by mouth twice per day for 7 days

OTHERPlacebo

Placebo (for POMx, containing no antioxidant contents; 1g) capsule by mouth twice per day for 7 days

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 89 Years

Healthy volunteers

Inclusion criteria

* Suffered an ischemic stroke and admitted to LLUMC Rehabilitation Institute for inpatient care * Fluent in English * Between the age of 18 and 89 years old

Exclusion criteria

* Less than 6 years of education * Global aphasia * Pregnant * History of allergy to pomegranates * History of traumatic brain injury * Neurodegenerative disease or neurologic condition with known cognitive impact (e.g., Alzheimer's disease) * Active renal disease * Active liver disease * Intracerebral hemorrhage in past 6 months * Neurosurgery in past month * Taking warfarin (Coumadin)

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score	Baseline and Day 9	The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) provides both a total scale score and scores for 5 different cognitive domains. It is relatively brief (approximately 20 minutes total) and has alternate forms. Specifically, the test measures immediate memory (with list learning and story memory), visuospatial/constructional ability (with figure copy and line orientation), language (with picture naming and semantic fluency), attention (with digit span and coding), and delayed memory (with list recall, list recognition, story recall, and figure recall). Scores from all subtests are aggregated into a total composite score (manual provides conversion procedure). RBANS data were age-normed based on the sample described in the manual (Randolph, 2012) and were analyzed as index scores (also referred to as standard scores), which have a mean of 100 and a standard deviation of 15. Higher scores on each sub measure and index indicate better performance.

Secondary

Measure	Time frame	Description
Change From Baseline Functional Independence Measure (FIM) Score	Baseline and Day 9	Functional Independence Measure (FIM) Score consists of eighteen sub-measures under the following 6 categories: Self-Care (eating, grooming, bathing, dressing upper body, dressing lower body, toileting), Sphincter Control (bladder control, bowel control), Transfers (bed/chair/wheelchair transfer, toilet transfer, tub/shower transfer), Locomotion (walk/wheelchair, stairs), Communication (comprehension, expression), and Social Cognition (social interaction, memory, problem solving). Scores for each sub-measure range from 1 (total assistance) to 7 (complete independence), and the 18 scores are summed to obtain the FIM score. Higher scores indicate better performance.
Change From Baseline Trail-making Test Part A Score	Baseline and Day 9	The Trail-making Test consists of 25 circles distributed over a sheet of paper. In Part A, the circles are numbered 1 - 25, and the patient should draw lines to connect the numbers in ascending order. Results for the test are reported as the number of seconds required to complete the task (ranges from 0 to 300; discontinued at 300 seconds); therefore, higher scores reveal greater impairment.
Change From Baseline Brief Test of Attention Score	Baseline and Day 9	On the Brief Test of Attention (BTA), the examinee listens to a string of numbers and letters and must mentally tally (without the use of their fingers) how many numbers are in a particular trial. They do this for 10 trials and then are given 10 additional trials with the task of tallying how many letters they hear. The task increases in difficulty as the trials progress, and the entire test takes 5-10 minutes to complete. The scorer adds the number of trials correct from all 20 trials to attain a total score (ranges from 0 to 20). Higher scores indicate better performance.
Change From Baseline Controlled Oral Word Association Test Score	Baseline and Day 9	The Controlled Oral Word Association Test (COWAT) is a measure of controlled verbal fluency that involves the examinee naming as many words that begin with a certain letter of the alphabet as he or she can in 1 minute. There are a few rules (i.e., no proper nouns and no words that have the same meaning and only differ by its suffix) and the task is repeated twice more with different letters each time. The scorer tallies the total acceptable words from all 3 trials into one total score (ranges from 0 on up). Higher total score indicates better performance.
Change From Baseline Line Bisection Test Score	Baseline and Day 9	The Line Bisection Test consists of 20 horizontal lines of varying length and proximity to the center of a sheet of paper (i.e., some are closer to the left or right sides of the page). The examinee is asked to place a mark to bisect each line. The scorer measures the degree of deviation from the center of each line (in cm) and attains the absolute value of the average percentage of deviation across all 20 lines. The scorer also attains the dominant direction of deviation (i.e., whether the examinee misses more to the left or to the right on average across the 20 lines). The value of the largest deviation is imputed for any omissions. Percentage ranges from 0 on up. Higher percentage of deviation indicates worse performance.
Change From Baseline Mini-Mental State Examination - 2nd Edition Score	Baseline and Day 9	The MMSE-2 is a brief (about 10 minutes) screening tool that touches upon orientation to time and place, recall, attention/calculation, naming, repetition, comprehension, reading, writing, and drawing, with all the scores from these domains cumulating to a maximum of 30 points (minimum = 0). Higher score indicates better performance.
Change From Baseline Animals Fluency Score	Baseline and Day 9	The Animal Fluency task involves providing the examinee a category prompt. For example, the examiner asks the examinee to name as many animals as he or she can in 1 minute. The total number of acceptable words is tallied for a total score (ranging from 0 on up). Higher scores indicate better performance.
Change From Baseline Beck Depression Inventory - II (BDI-II) Score	Baseline and Day 9	The Beck Depression Inventory - Second Edition (BDI-II) is a widely used self-report questionnaire of depressive symptoms. The examinee is asked to respond to 21 items by endorsing whether or not they experience symptoms of sadness, pessimism, past failure, loss of pleasure, guilty feelings, punishment feelings, self-dislike, self-criticalness, suicidal thoughts or wishes, crying, agitation, loss of interest, indecisiveness, worthlessness, loss of energy, changes in sleeping pattern, irritability, changes in appetite, concentrating difficulty, tiredness or fatigue, and loss of interest in sex. Examinees can also describe the degree of severity of each symptom, as each item ranges from 0-3. The scorer adds the scores for each item to attain a total score, which is interpreted according to the following guidelines: 0-13 = minimal depression, 14-19 = mild depression, 20-28 = moderate depression, 29-63 = severe depression
Change From Baseline State-Trait Anxiety Inventory - State Score	Baseline and Day 9	The State-Trait Anxiety Inventory (STAI) is a self-report inventory of anxiety symptoms. The test consists of two parts: 20 questions that assess anxiety level at the time of the examination (i.e., state) and 20 questions that assess the examinee's general level of anxiety (i.e., trait). Items include feeling at ease, feeling upset, feeling self-confident, feeling confused, feeling like a failure, feeling rested, and having disturbing thoughts, among others. Examinees endorse 1 of 4 options on a likert scale, from not at all to very much so. Each of the scales (state and trait) ranges from 0 to 80. Higher score indicates more anxiety symptoms.
Change From Baseline State-Trait Anxiety Inventory - Trait Score	Baseline and Day 9	The State-Trait Anxiety Inventory (STAI) is a self-report inventory of anxiety symptoms. The test consists of two parts: 20 questions that assess anxiety level at the time of the examination (i.e., state) and 20 questions that assess the examinee's general level of anxiety (i.e., trait). Items include feeling at ease, feeling upset, feeling self-confident, feeling confused, feeling like a failure, feeling rested, and having disturbing thoughts, among others. Examinees endorse 1 of 4 options on a likert scale, from not at all to very much so. Each of the scales (state and trait) ranges from 0 to 80. Higher score indicates more anxiety symptoms.
Change From Baseline Trail-making Test Part B Score	Baseline and Day 9	The Trail-making Test Part B consists of circles with either numbers (1 - 13) or letters (A - L) in them; as in Part A, the patient draws lines to connect the circles in an ascending pattern, but with the added task of alternating between the numbers and letters (i.e., 1-A-2-B-3-C, etc.). Results for both TMT A and B are reported as the number of seconds required to complete the task (ranges from 0 to 300; discontinued at 300 seconds); therefore, higher scores reveal greater impairment.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Stroke - POMx Pomegranate supplement (1g) by mouth twice per day for 7 days	8
Stroke - Placebo Placebo (for POMx, containing no antioxidant contents; 1g) capsule by mouth twice per day for 7 days	8
Total	16

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	1	0
Overall Study	Withdrawal by Subject	0	1

Baseline characteristics

Characteristic	Stroke - POMx	Stroke - Placebo	Total
Age, Continuous	58.13 years STANDARD_DEVIATION 13.62	59.63 years STANDARD_DEVIATION 13.48	58.88 years STANDARD_DEVIATION 13.11
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Black or African American	3 Participants	1 Participants	4 Participants
Race (NIH/OMB) More than one race	1 Participants	1 Participants	2 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	4 Participants	5 Participants	9 Participants
Region of Enrollment United States	8 participants	8 participants	16 participants
Sex: Female, Male Female	2 Participants	3 Participants	5 Participants
Sex: Female, Male Male	6 Participants	5 Participants	11 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	1 / 8	0 / 8
serious Total, serious adverse events	0 / 8	0 / 8

Outcome results

Primary

Change From Baseline Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score

The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) provides both a total scale score and scores for 5 different cognitive domains. It is relatively brief (approximately 20 minutes total) and has alternate forms. Specifically, the test measures immediate memory (with list learning and story memory), visuospatial/constructional ability (with figure copy and line orientation), language (with picture naming and semantic fluency), attention (with digit span and coding), and delayed memory (with list recall, list recognition, story recall, and figure recall). Scores from all subtests are aggregated into a total composite score (manual provides conversion procedure). RBANS data were age-normed based on the sample described in the manual (Randolph, 2012) and were analyzed as index scores (also referred to as standard scores), which have a mean of 100 and a standard deviation of 15. Higher scores on each sub measure and index indicate better performance.