Trial Outcomes & Findings for Cognitive Impact of Pomegranate Polyphenols Following Ischemic Stroke (NCT NCT02442804)

NCT ID: NCT02442804

Last Updated: 2017-08-02

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 16 participants
• Primary outcome timeframe: Baseline and Day 9
• Results posted on: 2017-08-02

Participant Flow

Participant milestones

Measure	Stroke - POMx Pomegranate supplement (1g) by mouth twice per day for 7 days	Stroke - Placebo Placebo (for POMx, containing no antioxidant contents; 1g) capsule by mouth twice per day for 7 days
Overall Study STARTED	8	8
Overall Study COMPLETED	7	7
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Measure	Stroke - POMx Pomegranate supplement (1g) by mouth twice per day for 7 days	Stroke - Placebo Placebo (for POMx, containing no antioxidant contents; 1g) capsule by mouth twice per day for 7 days
Overall Study Withdrawal by Subject	0	1
Overall Study Adverse Event	1	0

Baseline Characteristics

Cognitive Impact of Pomegranate Polyphenols Following Ischemic Stroke

Baseline characteristics by cohort

Measure	Stroke - POMx n=8 Participants Pomegranate supplement (1g) by mouth twice per day for 7 days	Stroke - Placebo n=8 Participants Placebo (for POMx, containing no antioxidant contents; 1g) capsule by mouth twice per day for 7 days	Total n=16 Participants Total of all reporting groups
Age, Continuous	58.13 years STANDARD_DEVIATION 13.62 • n=5 Participants	59.63 years STANDARD_DEVIATION 13.48 • n=7 Participants	58.88 years STANDARD_DEVIATION 13.11 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	8 participants n=5 Participants	8 participants n=7 Participants	16 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Stroke - POMx n=7 Participants Pomegranate supplement (1g) by mouth twice per day for 7 days	Stroke - Placebo n=7 Participants Placebo (for POMx, containing no antioxidant contents; 1g) capsule by mouth twice per day for 7 days
Change From Baseline Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Score	6.86 standard score change Standard Deviation 6.52	1.29 standard score change Standard Deviation 6.65

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Stroke - POMx n=7 Participants Pomegranate supplement (1g) by mouth twice per day for 7 days	Stroke - Placebo n=7 Participants Placebo (for POMx, containing no antioxidant contents; 1g) capsule by mouth twice per day for 7 days
Change From Baseline Mini-Mental State Examination - 2nd Edition Score	0.83 raw score Standard Deviation 2.48	0.43 raw score Standard Deviation 2.64

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Stroke - POMx n=8 Participants Pomegranate supplement (1g) by mouth twice per day for 7 days	Stroke - Placebo n=8 Participants Placebo (for POMx, containing no antioxidant contents; 1g) capsule by mouth twice per day for 7 days
Change From Baseline Functional Independence Measure (FIM) Score	22.63 raw score Standard Deviation 15.17	7.25 raw score Standard Deviation 6.82

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Stroke - POMx n=7 Participants Pomegranate supplement (1g) by mouth twice per day for 7 days	Stroke - Placebo n=7 Participants Placebo (for POMx, containing no antioxidant contents; 1g) capsule by mouth twice per day for 7 days
Change From Baseline Trail-making Test Part A Score	-18.14 seconds Standard Deviation 18.8	-19.86 seconds Standard Deviation 33.35

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Stroke - POMx n=7 Participants Pomegranate supplement (1g) by mouth twice per day for 7 days	Stroke - Placebo n=7 Participants Placebo (for POMx, containing no antioxidant contents; 1g) capsule by mouth twice per day for 7 days
Change From Baseline Brief Test of Attention Score	3.29 raw score Standard Deviation 1.38	0.14 raw score Standard Deviation 2.41

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Stroke - POMx n=7 Participants Pomegranate supplement (1g) by mouth twice per day for 7 days	Stroke - Placebo n=7 Participants Placebo (for POMx, containing no antioxidant contents; 1g) capsule by mouth twice per day for 7 days
Change From Baseline Controlled Oral Word Association Test Score	1.29 number of acceptable words Standard Deviation 2.43	2.14 number of acceptable words Standard Deviation 3.67

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Stroke - POMx n=7 Participants Pomegranate supplement (1g) by mouth twice per day for 7 days	Stroke - Placebo n=7 Participants Placebo (for POMx, containing no antioxidant contents; 1g) capsule by mouth twice per day for 7 days
Change From Baseline Line Bisection Test Score	-0.91 percentage of deviation from center Standard Deviation 3.79	-3.71 percentage of deviation from center Standard Deviation 4.69

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Stroke - POMx n=7 Participants Pomegranate supplement (1g) by mouth twice per day for 7 days	Stroke - Placebo n=7 Participants Placebo (for POMx, containing no antioxidant contents; 1g) capsule by mouth twice per day for 7 days
Change From Baseline Trail-making Test Part B Score	-20 seconds Standard Deviation 21.03	-39 seconds Standard Deviation 39.64

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Stroke - POMx n=7 Participants Pomegranate supplement (1g) by mouth twice per day for 7 days	Stroke - Placebo n=7 Participants Placebo (for POMx, containing no antioxidant contents; 1g) capsule by mouth twice per day for 7 days
Change From Baseline Animals Fluency Score	-0.14 number of acceptable words (animals) Standard Deviation 2.19	3.14 number of acceptable words (animals) Standard Deviation 2.67

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Stroke - POMx n=7 Participants Pomegranate supplement (1g) by mouth twice per day for 7 days	Stroke - Placebo n=7 Participants Placebo (for POMx, containing no antioxidant contents; 1g) capsule by mouth twice per day for 7 days
Change From Baseline Beck Depression Inventory - II (BDI-II) Score	0.14 raw score Standard Deviation 9.58	-3.86 raw score Standard Deviation 9.48

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Stroke - POMx n=7 Participants Pomegranate supplement (1g) by mouth twice per day for 7 days	Stroke - Placebo n=7 Participants Placebo (for POMx, containing no antioxidant contents; 1g) capsule by mouth twice per day for 7 days
Change From Baseline State-Trait Anxiety Inventory - State Score	-5.86 raw score Standard Deviation 10.43	-2.86 raw score Standard Deviation 12.62

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Stroke - POMx n=7 Participants Pomegranate supplement (1g) by mouth twice per day for 7 days	Stroke - Placebo n=7 Participants Placebo (for POMx, containing no antioxidant contents; 1g) capsule by mouth twice per day for 7 days
Change From Baseline State-Trait Anxiety Inventory - Trait Score	-1.57 raw score Standard Deviation 7.87	-1 raw score Standard Deviation 9.17

Adverse Events

Stroke - POMx

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Stroke - Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Stroke - POMx n=8 participants at risk Pomegranate supplement (1g) by mouth twice per day for 7 days	Stroke - Placebo n=8 participants at risk Placebo (for POMx, containing no antioxidant contents; 1g) capsule by mouth twice per day for 7 days
Psychiatric disorders Psychotic Episode	12.5% 1/8 • Number of events 1	0.00% 0/8

Additional Information

John Bellone, Ph.D.

Brown University

Phone: 4012737100

Email: john_bellone@brown.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place