Trial Outcomes & Findings for COGNUTRIN in Breast Cancer Survivors (NCT NCT01823991)

NCT ID: NCT01823991

Last Updated: 2020-07-14

Results Overview

Mean change in cognitive function scores measured from baseline to post intervention with Cognutrin compared to placebo. Mean cognitive function scores by group and compared by time of testing (Time 1, Time 2). The HVLT test assesses verbal learning and memory. Subjects are given a list of words and asked to repeat as many words as they can recall at 3 times. There is no absolute low \& high, as scores are age adjusted. Reported scores are T-scores- average score should be 50, with a standard deviation of 10. Any score below 50 indicates performance below population averages and any score above 50 indicates higher than population averages.The COWA test is a verbal fluency test that measures spontaneous production of words belonging to the same category or beginning with a designed letter. The scores are converted to z-scores. A Z score of -1 is 1 standard deviation below mean. The lowest and highest Z scores could be ≤ -3.0 and ≥3.0. A lower Z score is indicative of poor fluency.

Recruitment status

COMPLETED

Study phase

EARLY_PHASE1

Target enrollment

36 participants

Primary outcome timeframe

Baseline (Time 1) and at 3 months +/- 7 days (Time 2)

Results posted on

2020-07-14

Participant Flow

Participants were enrolled at Moffitt Cancer Center between July 2014 and February 2017.

Participants were randomized to receive Cognutrin (n-3 fatty acids + anthocyanins) or placebo for a period of 3 months.

Participant milestones

Participant milestones
Measure
COGNUTRIN (n-3 Fatty Acids + Anthocynins) Twice a Day (BID)
Participants will be provided with two bottles containing Lovaza and VitaBlue. Participants will be asked to take 1 tablet of Lovaza two times a day and 1 tablet of VitaBlue three times a day. VitaBlue™: Self administration of nutritional supplement COGNUTRIN for 3 months. The supplement to be used will be a combination of the following: (1) VitaBlue (40% polyphenolics, 12.5% anthocyanins from blueberries (BB) and (2) n-3 fatty acids - Lovaza. Lovaza®: Self administration of nutritional supplement COGNUTRIN for 3 months. The supplement to be used will be a combination of the following: (1) VitaBlue (40% polyphenolics, 12.5% anthocyanins from blueberries (BB) and (2) n-3 fatty acids - Lovaza.
Matching Placebo BID
Participants will be provided with two bottles containing placebos. Participants will be asked to take 1 tablet of placebo two times a day and 1 tablet of or placebo three times a day. Placebo: Self administration of placebo for 3 months. Investigators use a placebo to make sure that it really is the study medicine that is making a difference in the participant's condition. It does not have anything in it that would normally help or harm most people.
Overall Study
STARTED
18
18
Overall Study
COMPLETED
10
13
Overall Study
NOT COMPLETED
8
5

Reasons for withdrawal

Reasons for withdrawal
Measure
COGNUTRIN (n-3 Fatty Acids + Anthocynins) Twice a Day (BID)
Participants will be provided with two bottles containing Lovaza and VitaBlue. Participants will be asked to take 1 tablet of Lovaza two times a day and 1 tablet of VitaBlue three times a day. VitaBlue™: Self administration of nutritional supplement COGNUTRIN for 3 months. The supplement to be used will be a combination of the following: (1) VitaBlue (40% polyphenolics, 12.5% anthocyanins from blueberries (BB) and (2) n-3 fatty acids - Lovaza. Lovaza®: Self administration of nutritional supplement COGNUTRIN for 3 months. The supplement to be used will be a combination of the following: (1) VitaBlue (40% polyphenolics, 12.5% anthocyanins from blueberries (BB) and (2) n-3 fatty acids - Lovaza.
Matching Placebo BID
Participants will be provided with two bottles containing placebos. Participants will be asked to take 1 tablet of placebo two times a day and 1 tablet of or placebo three times a day. Placebo: Self administration of placebo for 3 months. Investigators use a placebo to make sure that it really is the study medicine that is making a difference in the participant's condition. It does not have anything in it that would normally help or harm most people.
Overall Study
Withdrawal by Subject
8
5

Baseline Characteristics

COGNUTRIN in Breast Cancer Survivors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
COGNUTRIN (n-3 Fatty Acids + Anthocynins) Twice a Day (BID)
n=18 Participants
Participants will be provided with two bottles containing Lovaza (or placebo) and VitaBlue (or placebo). Participants will be asked to take 1 tablet of Lovaza (or placebo) two times a day and 1 tablet of VitaBlue (or placebo) three times a day. VitaBlue™: Self administration of nutritional supplement COGNUTRIN for 3 months. The supplement to be used will be a combination of the following: (1) VitaBlue (40% polyphenolics, 12.5% anthocyanins from blueberries (BB) and (2) n-3 fatty acids - Lovaza. Lovaza®: Self administration of nutritional supplement COGNUTRIN for 3 months. The supplement to be used will be a combination of the following: (1) VitaBlue (40% polyphenolics, 12.5% anthocyanins from blueberries (BB) and (2) n-3 fatty acids - Lovaza.
Matching Placebo BID
n=18 Participants
Participants will be provided with two bottles containing Lovaza (or placebo) and VitaBlue (or placebo). Participants will be asked to take 1 tablet of Lovaza (or placebo) two times a day and 1 tablet of VitaBlue (or placebo) three times a day. Placebo: Self administration of placebo for 3 months. Investigators use a placebo to make sure that it really is the study medicine that is making a difference in the participant's condition. It does not have anything in it that would normally help or harm most people.
Total
n=36 Participants
Total of all reporting groups
Age, Continuous
43.7 years
STANDARD_DEVIATION 4.85 • n=5 Participants
50.92 years
STANDARD_DEVIATION 6.17 • n=7 Participants
46 years
STANDARD_DEVIATION 7.9 • n=5 Participants
Sex: Female, Male
Female
18 Participants
n=5 Participants
18 Participants
n=7 Participants
36 Participants
n=5 Participants
Sex: Female, Male
Male
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 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
2 Participants
n=5 Participants
2 Participants
n=7 Participants
4 Participants
n=5 Participants
Race (NIH/OMB)
White
16 Participants
n=5 Participants
15 Participants
n=7 Participants
31 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 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
18 participants
n=5 Participants
18 participants
n=7 Participants
36 participants
n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Time 1) and at 3 months +/- 7 days (Time 2)

Population: All evaluable participants at time of analysis.

Mean change in cognitive function scores measured from baseline to post intervention with Cognutrin compared to placebo. Mean cognitive function scores by group and compared by time of testing (Time 1, Time 2). The HVLT test assesses verbal learning and memory. Subjects are given a list of words and asked to repeat as many words as they can recall at 3 times. There is no absolute low \& high, as scores are age adjusted. Reported scores are T-scores- average score should be 50, with a standard deviation of 10. Any score below 50 indicates performance below population averages and any score above 50 indicates higher than population averages.The COWA test is a verbal fluency test that measures spontaneous production of words belonging to the same category or beginning with a designed letter. The scores are converted to z-scores. A Z score of -1 is 1 standard deviation below mean. The lowest and highest Z scores could be ≤ -3.0 and ≥3.0. A lower Z score is indicative of poor fluency.

Outcome measures

Outcome measures
Measure
A - Cognutrin #1
n=5 Participants
Cognutrin Treatment Time 1
B - Cognutrin #2
n=5 Participants
Cognutrin Time 2.
C - Placebo #1
n=10 Participants
Placebo Time 1.
D - Placebo #2
n=10 Participants
Placebo Time 2.
Change in Cognitive Function Scores With Intervention - HVLT and COWA
HVLT-total recall
49.04 score
Standard Error 6.41
44.93 score
Standard Error 7.55
42.28 score
Standard Error 4.21
43.33 score
Standard Error 4.96
Change in Cognitive Function Scores With Intervention - HVLT and COWA
COWA-z score
-.341 score
Standard Error .686
-.452 score
Standard Error .577
-0.001 score
Standard Error 0.451
0.332 score
Standard Error 0.379
Change in Cognitive Function Scores With Intervention - HVLT and COWA
HVLT-delayed recall
44.82 score
Standard Error 5.33
41.59 score
Standard Error 7.02
47.49 score
Standard Error 3.5
44.1 score
Standard Error 4.62

PRIMARY outcome

Timeframe: Baseline (Time 1) and at 3 months +/- 7 days (Time 2)

Population: All evaluable participants at time of analysis.

Mean change in cognitive function scores measured from baseline to post intervention with Cognutrin compared to placebo arms of the trial. Mean cognitive function scores by group and compared by time of testing (Time 1, Time 2). Tests: Color Trails 1 \& Color Trails 2. Color Trails 1 consists of a page with scattered circles numbered from 1-25. Even numbered circles are colored yellow and odd numbered ones are colored pink. Respondents are instructed to connect the circles in consecutive numeric order with a continuous line as quickly as possible. Score is determined by recording the number of seconds required to complete the task. Color Trails 2 consists of a page containing 25 pink circles and 25 yellow circles numbered 1-60. Respondents are instructed to connect circles in consecutive order while alternating colors. A total score is determined by recording the number of seconds required to compete the task.

Outcome measures

Outcome measures
Measure
A - Cognutrin #1
n=4 Participants
Cognutrin Treatment Time 1
B - Cognutrin #2
n=4 Participants
Cognutrin Time 2.
C - Placebo #1
n=10 Participants
Placebo Time 1.
D - Placebo #2
n=10 Participants
Placebo Time 2.
Change in Cognitive Function Scores With Intervention - Color Trails 1 & 2
Color Trails 1
59.82 seconds
Standard Error 11.5
61.25 seconds
Standard Error 4.87
47.47 seconds
Standard Error 2.89
50.80 seconds
Standard Error 2.76
Change in Cognitive Function Scores With Intervention - Color Trails 1 & 2
Color Trails 2
60.35 seconds
Standard Error 4.35
60.57 seconds
Standard Error 4.64
54.96 seconds
Standard Error 2.47
59.97 seconds
Standard Error 2.63

PRIMARY outcome

Timeframe: Baseline (Time 1) and at 3 months +/- 7 days (Time 2)

Population: All evaluable participants at time of analysis.

Mean change in cognitive function scores measured from baseline to post intervention with Cognutrin compared to placebo. Mean cognitive function scores by group and compared by time of testing (Time 1, Time 2). The Digit Span assesses immediate verbal memory and auditory attention. The examiner reads increasingly longer series of numbers and the respondent is required to repeat them in the same order. The examiner then reads additional sequences of numbers and the respondent is required to repeat them in reverse order. Digit Span yields one score, number of items completed correctly. Scores are scaled from the Wechsler Adult Intelligence Scale. The values for these scaled scores indicated that values from 1-7 indicate below average performance, corresponding to 1-16 percentile ranks. Scores between 8-12 indicate average performance, corresponding to percentile ranks of 25-75. Scores between 13-19 correspond to areas of strength and 84-99 percentile ranks.

Outcome measures

Outcome measures
Measure
A - Cognutrin #1
n=5 Participants
Cognutrin Treatment Time 1
B - Cognutrin #2
n=5 Participants
Cognutrin Time 2.
C - Placebo #1
n=11 Participants
Placebo Time 1.
D - Placebo #2
n=11 Participants
Placebo Time 2.
Change in Cognitive Function Scores With Intervention - Digit Span
9.58 score
Standard Error 1.43
12.69 score
Standard Error 1.75
10.01 score
Standard Error .89
10.05 score
Standard Error 1.09

PRIMARY outcome

Timeframe: Baseline (Time 1) and at 3 months +/- 7 days (Time 2)

Population: All evaluable participants at time of analysis.

Mean change in cognitive function scores measured from baseline to post intervention with Cognutrin compared to placebo arms of the trial. Mean cognitive function scores by group and compared by time of testing (Time 1, Time 2). The Symbol Digit Modalities Test requires respondents to write the number that corresponds with each symbol for a series of 110 items in which the symbol but not the number appears. Respondents identify the correct number using a key provided in which symbols are matched with numbers. Total score is determined by calculating the number of items correctly completed in 90 seconds Scale uses z-scores which have a mean of 0 and a standard deviation of 1. Scores cores above 0 indicate better than average performance whereas scores below 0 indicate poorer than average performance.

Outcome measures

Outcome measures
Measure
A - Cognutrin #1
n=4 Participants
Cognutrin Treatment Time 1
B - Cognutrin #2
n=4 Participants
Cognutrin Time 2.
C - Placebo #1
n=11 Participants
Placebo Time 1.
D - Placebo #2
n=11 Participants
Placebo Time 2.
Change in Cognitive Function Scores With Intervention - Symbol Digit Modalities Test
.17 score
Standard Error .72
.39 score
Standard Error .62
.53 score
Standard Error .39
.72 score
Standard Error .33

SECONDARY outcome

Timeframe: 3 months from baseline +/- 7 days

Population: All evaluable participants who received treatment.

The primary safety endpoint is incidence and severity of AEs occurring during intervention with either COGNUTRIN or placebo. All AEs that are reported by the participant, detected during a visit, physical examination, or laboratory work-up will be recorded in the participant's medical record and recorded on the case report form (CRF). All AEs that occur after the informed consent is signed will be recorded on the AE CRF whether or not related to study agent, using the NCI Common Terminology Criteria for AEs (CTCAE) version 4.0.

Outcome measures

Outcome measures
Measure
A - Cognutrin #1
n=16 Participants
Cognutrin Treatment Time 1
B - Cognutrin #2
n=16 Participants
Cognutrin Time 2.
C - Placebo #1
Placebo Time 1.
D - Placebo #2
Placebo Time 2.
Number of Participants With Adverse Events (AEs)
10 Participants
4 Participants

SECONDARY outcome

Timeframe: 3 months from baseline +/- 7 days

Population: Participants with Adverse Events.

Number of Adverse events according to relation to study treatment category: Definitely related, Probably related, Possibly related, Unlikely to be related, Unrelated.

Outcome measures

Outcome measures
Measure
A - Cognutrin #1
n=10 Participants
Cognutrin Treatment Time 1
B - Cognutrin #2
n=4 Participants
Cognutrin Time 2.
C - Placebo #1
Placebo Time 1.
D - Placebo #2
Placebo Time 2.
Occurrence of Adverse Events (AEs) by Causality
Definitely related to treatment
5 Adverse Events
0 Adverse Events
Occurrence of Adverse Events (AEs) by Causality
Probably related to treatment
1 Adverse Events
0 Adverse Events
Occurrence of Adverse Events (AEs) by Causality
Possibly related to treatment
0 Adverse Events
0 Adverse Events
Occurrence of Adverse Events (AEs) by Causality
Unlikely to be related to treatment
0 Adverse Events
0 Adverse Events
Occurrence of Adverse Events (AEs) by Causality
Unrelated to treatment
11 Adverse Events
8 Adverse Events

SECONDARY outcome

Timeframe: 3 months from baseline +/- 7 days

Population: Evaluable participants who received treatment.

The primary safety endpoint is incidence and severity of AEs occurring during intervention with either COGNUTRIN or placebo. All AEs that are reported by the subject, detected during a visit, physical examination, or laboratory work-up will be recorded in the participant's medical record and recorded on the case report form (CRF). All AEs that occur after the informed consent is signed will be recorded on the AE CRF whether or not related to study agent, using the NCI Common Terminology Criteria for AEs (CTCAE) version 4.0.

Outcome measures

Outcome measures
Measure
A - Cognutrin #1
n=16 Participants
Cognutrin Treatment Time 1
B - Cognutrin #2
n=16 Participants
Cognutrin Time 2.
C - Placebo #1
Placebo Time 1.
D - Placebo #2
Placebo Time 2.
Number of Participants Experiencing Grade 3 or Higher Adverse Events
0 participants
0 participants

SECONDARY outcome

Timeframe: 3 months

Population: All participants with both pre- and post-therapy brain MRI examinations.

Functional: Improved cortical activation in multiple areas of the brain on examination of functional MRI post study intervention. Imaging including: 1) Extended resting state functional MRI with data post-processed on Philips EWS. Performed with patient's eyes closed and minds wandering. 2) Diffusion tensor imaging (DTI) with effective slice thickness of 2.3mm. Post-processed on Philips EWS with color-coded DTI tractography images obtained, absolute FA calculations performed in 9 anatomic areas in both right and left brain with total of 18 FA values obtained per examination. Structural: Improved white matter signal changes which correlate with ischemic changes or microvascular ischemic changes, cortical atrophy, hippocampal atrophy, brain volume and gray-white matter ratio. Anatomic sequences including: 1) Coronal 3-D volume T1 weighted gradient echo images with effective slice thickness of 1mm. 2) Axial FLAIR (fluid attenuated inversion recovery)

Outcome measures

Outcome measures
Measure
A - Cognutrin #1
n=7 Participants
Cognutrin Treatment Time 1
B - Cognutrin #2
n=8 Participants
Cognutrin Time 2.
C - Placebo #1
Placebo Time 1.
D - Placebo #2
Placebo Time 2.
Number of Participants With Improvement in Function MRI and Structural MRI Post-Intervention
Functional MRI
2 Participants
0 Participants
Number of Participants With Improvement in Function MRI and Structural MRI Post-Intervention
Structural MRI
0 Participants
0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 3 months

Population: All evaluable participants at time of analysis

Mean change plasma cytokines from baseline to post intervention with Cognutrin vs. placebo. Inflammatory markers-Cytokines were measured with a panel including IFN-g, IL-6, IL-8 and INF-alpha.

Outcome measures

Outcome measures
Measure
A - Cognutrin #1
n=5 Participants
Cognutrin Treatment Time 1
B - Cognutrin #2
n=5 Participants
Cognutrin Time 2.
C - Placebo #1
n=9 Participants
Placebo Time 1.
D - Placebo #2
n=9 Participants
Placebo Time 2.
Change in Plasma Cytokines
IFN-g
6.23 pg/mL
Standard Error 2.3
8.3 pg/mL
Standard Error 2.48
6.2 pg/mL
Standard Error 1.72
4.64 pg/mL
Standard Error 1.85
Change in Plasma Cytokines
IL-10
0.29 pg/mL
Standard Error 0.07
0.2 pg/mL
Standard Error 0.03
0.18 pg/mL
Standard Error 0.05
0.22 pg/mL
Standard Error 0.03
Change in Plasma Cytokines
IL-6
0.55 pg/mL
Standard Error 0.21
2.07 pg/mL
Standard Error 1.05
1.14 pg/mL
Standard Error 0.16
1.5 pg/mL
Standard Error 0.78
Change in Plasma Cytokines
IL-8
5.56 pg/mL
Standard Error 0.92
8.55 pg/mL
Standard Error 2
7.82 pg/mL
Standard Error 0.69
8.02 pg/mL
Standard Error 1.49
Change in Plasma Cytokines
INF-α
2.29 pg/mL
Standard Error 0.19
2.53 pg/mL
Standard Error 0.36
2.61 pg/mL
Standard Error 0.14
2.61 pg/mL
Standard Error 2.61

Adverse Events

Cognutrin (n-3 Fatty Acids + Anthocyanins) Twice a Day (BID)

Serious events: 1 serious events
Other events: 10 other events
Deaths: 0 deaths

Matching Placebo Twice a Day (BID)

Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Cognutrin (n-3 Fatty Acids + Anthocyanins) Twice a Day (BID)
n=18 participants at risk
Self administration of nutritional supplement COGNUTRIN for 3 months.
Matching Placebo Twice a Day (BID)
n=18 participants at risk
Self administration of placebo for 3 months.
Psychiatric disorders
Psychosis
5.6%
1/18 • Number of events 1 • 2 years, 10 months
0.00%
0/18 • 2 years, 10 months

Other adverse events

Other adverse events
Measure
Cognutrin (n-3 Fatty Acids + Anthocyanins) Twice a Day (BID)
n=18 participants at risk
Self administration of nutritional supplement COGNUTRIN for 3 months.
Matching Placebo Twice a Day (BID)
n=18 participants at risk
Self administration of placebo for 3 months.
Gastrointestinal disorders
Nausea
16.7%
3/18 • Number of events 3 • 2 years, 10 months
5.6%
1/18 • Number of events 1 • 2 years, 10 months
Gastrointestinal disorders
Gastrointestinal disorders - Other
16.7%
3/18 • Number of events 3 • 2 years, 10 months
0.00%
0/18 • 2 years, 10 months
Gastrointestinal disorders
Vomiting
11.1%
2/18 • Number of events 3 • 2 years, 10 months
0.00%
0/18 • 2 years, 10 months
Gastrointestinal disorders
Abdominal pain
0.00%
0/18 • 2 years, 10 months
5.6%
1/18 • Number of events 2 • 2 years, 10 months
Gastrointestinal disorders
Constipation
5.6%
1/18 • Number of events 1 • 2 years, 10 months
0.00%
0/18 • 2 years, 10 months
Gastrointestinal disorders
Diarrhea
5.6%
1/18 • Number of events 1 • 2 years, 10 months
0.00%
0/18 • 2 years, 10 months
General disorders
Flu like symptoms
11.1%
2/18 • Number of events 2 • 2 years, 10 months
0.00%
0/18 • 2 years, 10 months
General disorders
Chills
5.6%
1/18 • Number of events 1 • 2 years, 10 months
0.00%
0/18 • 2 years, 10 months
General disorders
Edema limbs
5.6%
1/18 • Number of events 1 • 2 years, 10 months
0.00%
0/18 • 2 years, 10 months
General disorders
Pain
5.6%
1/18 • Number of events 1 • 2 years, 10 months
0.00%
0/18 • 2 years, 10 months
Vascular disorders
Hot flashes
5.6%
1/18 • Number of events 1 • 2 years, 10 months
5.6%
1/18 • Number of events 1 • 2 years, 10 months
Vascular disorders
Flushing
5.6%
1/18 • Number of events 1 • 2 years, 10 months
0.00%
0/18 • 2 years, 10 months
Metabolism and nutrition disorders
Hyperkalemia
5.6%
1/18 • Number of events 1 • 2 years, 10 months
0.00%
0/18 • 2 years, 10 months
Metabolism and nutrition disorders
Metabolism and nutrition disorders, Other
0.00%
0/18 • 2 years, 10 months
5.6%
1/18 • Number of events 1 • 2 years, 10 months
Nervous system disorders
Headache
0.00%
0/18 • 2 years, 10 months
5.6%
1/18 • Number of events 1 • 2 years, 10 months
Nervous system disorders
Somnolence
0.00%
0/18 • 2 years, 10 months
5.6%
1/18 • Number of events 1 • 2 years, 10 months
Psychiatric disorders
Insomnia
5.6%
1/18 • Number of events 1 • 2 years, 10 months
0.00%
0/18 • 2 years, 10 months
Immune system disorders
Allergic reaction
0.00%
0/18 • 2 years, 10 months
5.6%
1/18 • Number of events 1 • 2 years, 10 months
Skin and subcutaneous tissue disorders
Rash acneiform
0.00%
0/18 • 2 years, 10 months
5.6%
1/18 • Number of events 1 • 2 years, 10 months

Additional Information

Dr. Nagi Kumar

H. Lee Moffitt Cancer Center and Research Institute

Phone: 813-745-6885

Results disclosure agreements

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