Cognitive Dysfunction
Conditions
Brief summary
Nine-weeks double-blind, randomized, placebo-controlled, parallel-arm superiority study. The aim of this study is to evaluate the influence of a mix of four bioactive compounds - bacopa, lycopene, astaxanthin and vitamin B12 - on cognitive performance, mood state and well-being in subjects aged ≥ 60 years with no evidence of cognitive dysfunction. The primary objective of the study is to evaluate the changes in Trial Making Test (TMT) scores from baseline (V2) to 8 weeks of treatment (V4), analyzed in the following hierarchical order: TMT-B, TMT-A and TMT B-A. Secondary objectives of this study are to evaluate changes from baseline (V2) to 8 weeks of treatment (V4) in Verbal Fluency Test (VFT) score, Montreal Cognitive Assessment (MoCA) score, Mini Mental State Examination (MMSE) score, Rey Auditory Verbal Learning Test (AVLT), psychological well-being as assessed by General Health Questionnaire (GHQ-12), mood states as assessed by the Profile of Mood Stated (POMS), sexual satisfaction as evaluated by the New Sexual Satisfaction Scale (NSSS). Changes of metabolic parameters from baseline (V2) to 4 weeks of treatment (V3) and from baseline (V2) to 8 weeks of treatment (V4) will be also evaluated as secondary objectives (glucose, insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, uric acid). Changes of plasma markers of oxidative stress from baseline (V2) to 4 weeks of treatment (V3) and from baseline (V2) to 8 weeks of treatment (V4) will be evaluated as secondary objectives (8-iso-Prostaglandin F2alpha, Plasma malondialdehyde). Finally the safety and tolerability of the study product will be assessed.
Detailed description
The study has been conducted in 1 Italian clinical site and involved 80 subjects. Subjects will be randomly allocated to one of the following groups: * Group I: mix of the four bioactive compounds (bacopa, lycopene, astaxanthin and vitamin B12), once a day for 8 weeks per os; * Group II: placebo, once a day for 8 weeks per os. The study is double blind. Neither the study staff at clinical sites (Investigators, nurses, pharmacist) nor the subject was aware of the treatment assigned. Each participant attended 4 visits over a total period of about 9 weeks.
Interventions
DIETARY_SUPPLEMENTA mix of bioactive natural compounds
A mix of bacopa, lycopene, astaxanthin and vitamin B12 in oral tablets
DIETARY_SUPPLEMENTPlacebo
Inactive compound in oral tablets
Sponsors
A. Menarini Industrie Farmaceutiche Riunite S.r.l.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The study treatment was assigned through envelopes randomization system: the site was provided with sealed envelopes, numbered in progressive number starting from R-001, containing the treatment kit to be assigned to the subject. The Investigator will open the first available envelope in progressive order. Inside the envelope there will be the kit number of the treatment to be assigned to that subject.
Intervention model description
9-weeks double-blind, randomized, placebo-controlled, parallel-arm superiority study
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subjects aged ≥60 years. 2. Subjects who provide written Informed Consent to the study.
Exclusion criteria
1. Subjects with cognitive dysfunctions or clinically significant coexisting medical conditions (cardiovascular disease, cerebrovascular events, overt dementia defined by MMSE \<27 or other neurological disorders, thyroid disorders, or inflammatory diseases) 2. Subjects with a score on the Geriatric Depression Scale (GDS) \>11 in order to avoid confounding due to the influence of concomitant depression on the performance on cognitive tests 3. Current smokers 4. Habitual users of antioxidant supplements (including vitamins C and E) 5. Habitual consumers of chocolate or other cocoa products (daily consumption of any amount) 6. Subjects under treatments with medications known to have antioxidant properties (including statins and glitazones) or to interfere with cognitive functions (including benzodiazepines and antidepressants) 7. Subjects with hypersensitivity to any component of the study medications 8. Subjects who are participating in or having participated in another clinical trial within the previous three months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Trail Making Test (TMT) B Between Baseline and End of Treatment | 8 weeks - from baseline to end of study | Change in Trail Making Test (TMT) B scores from baseline (V2) to 8 weeks of treatment (V4). The reduction in the number of seconds the patients take to make the test after the study treatment means an improvement in cognitive functions. |
| Change Trail Making Test (TMT) A Between Baseline and End of Treatment | 8 weeks - from baseline to end of study | Change in Trail Making Test (TMT) A scores from baseline (V2) to 8 weeks of treatment (V4). The reduction in the number of seconds the patients take to make the test after the study treatment means an improvement in cognitive functions. |
| Change in Trail Making Test (TMT) B - Trail Making Test (TMT) A Between Baseline and End of Treatment | 8 weeks - from baseline to end of study | Change in Trail Making Test (TMT) B score minus Trail Making Test (TMT) A score from baseline (V2) to 8 weeks of treatment (V4). The reduction in the number of seconds the patients take to make the test after the study treatment means an improvement in cognitive functions. |
Countries
Italy
Participant flow
Recruitment details
The recruitment period started on January 2018 and terminated on October 2018. A total of 80 subjetcs have been randomization and 78 completed the study. Each subject has been involved in the study for approximately two months. A total of 4 study visits has been performed for each subject.
Pre-assignment details
Subjects who provided written informed consent have been subjected to the screening assessments. Subjects who met all inclusion criteria and none of the exclusion criteria have been eligible for the study and have proceeded with the randomization visit after 7 days. No wash-out or run-in period was used in this study. 8
Participants by arm
| Arm | Count |
|---|---|
| Food Supplement A mix of bacopa, lycopene, astaxanthin and vitamin B12 Dosage form: tablets Dosage: 1 tablet per day Duration: 8 weeks
A mix of bioactive natural compounds: A mix of bacopa, lycopene, astaxanthin and vitamin B12 in oral tablets | 40 |
| Placebo Inactive compound Dosage form: tablets Dosage: 1 tablet per day Duration: 8 weeks
Placebo: Inactive compound in oral tablets | 40 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Food Supplement | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 1 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 37 Participants | 39 Participants | 76 Participants |
| Age, Continuous | 61.88 years STANDARD_DEVIATION 1.36 | 62.05 years STANDARD_DEVIATION 1.55 | 61.96 years STANDARD_DEVIATION 1.45 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 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 | 40 Participants | 40 Participants | 80 Participants |
| Region of Enrollment Italy | 40 participants | 40 participants | 80 participants |
| Sex: Female, Male Female | 28 Participants | 27 Participants | 55 Participants |
| Sex: Female, Male Male | 12 Participants | 13 Participants | 25 Participants |
| Trial Making Test (TMT) A | 25.17 seconds STANDARD_DEVIATION 10.53 | 24.20 seconds STANDARD_DEVIATION 7.37 | 24.68 seconds STANDARD_DEVIATION 8.95 |
| Trial Making Test (TMT) B | 56.97 seconds STANDARD_DEVIATION 25.37 | 54.64 seconds STANDARD_DEVIATION 21.3 | 55.80 seconds STANDARD_DEVIATION 23.33 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 40 |
| other Total, other adverse events | 1 / 40 | 0 / 40 |
| serious Total, serious adverse events | 1 / 40 | 0 / 40 |
Outcome results
Primary
Change in Trail Making Test (TMT) B Between Baseline and End of Treatment
Change in Trail Making Test (TMT) B scores from baseline (V2) to 8 weeks of treatment (V4). The reduction in the number of seconds the patients take to make the test after the study treatment means an improvement in cognitive functions.
Time frame: 8 weeks - from baseline to end of study
Population: Intention To Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Food Supplement | Change in Trail Making Test (TMT) B Between Baseline and End of Treatment | -17.63 seconds | Standard Deviation 18.93 |
| Placebo | Change in Trail Making Test (TMT) B Between Baseline and End of Treatment | 3.46 seconds | Standard Deviation 13.08 |
p-value: 095% CI: [-26.8, -15.2]ANCOVA
Primary
Change in Trail Making Test (TMT) B - Trail Making Test (TMT) A Between Baseline and End of Treatment
Change in Trail Making Test (TMT) B score minus Trail Making Test (TMT) A score from baseline (V2) to 8 weeks of treatment (V4). The reduction in the number of seconds the patients take to make the test after the study treatment means an improvement in cognitive functions.
Time frame: 8 weeks - from baseline to end of study
Population: Intention To Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Food Supplement | Change in Trail Making Test (TMT) B - Trail Making Test (TMT) A Between Baseline and End of Treatment | -10.46 seconds | Standard Deviation 16.62 |
| Placebo | Change in Trail Making Test (TMT) B - Trail Making Test (TMT) A Between Baseline and End of Treatment | 3.84 seconds | Standard Deviation 11.65 |
p-value: 095% CI: [-20.02, -9.11]ANCOVA
Primary
Change Trail Making Test (TMT) A Between Baseline and End of Treatment
Change in Trail Making Test (TMT) A scores from baseline (V2) to 8 weeks of treatment (V4). The reduction in the number of seconds the patients take to make the test after the study treatment means an improvement in cognitive functions.
Time frame: 8 weeks - from baseline to end of study
Population: Intention To Treat
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Food Supplement | Change Trail Making Test (TMT) A Between Baseline and End of Treatment | -6.86 seconds | Standard Deviation 10 |
| Placebo | Change Trail Making Test (TMT) A Between Baseline and End of Treatment | -0.37 seconds | Standard Deviation 5.31 |
p-value: 095% CI: [-8.45, -3.61]ANCOVA