Nutraceutical Effects on Long-Term Memory
Condition: Aging
Study type: Interventional
Phase: Phase 2

Summary: 
      Interventions to improve the cognitive health of older adults are of critical importance. In
      the current protocol, ithe investigators conducted a short-term (two months) randomized
      clinical trial to examine the influence of the nutraceutical NT-020 on the cognitive
      performance of older adults. Participants were tested with a battery of cognitive tasks at
      baseline and two months after being randomized to the interventional drug or placebo.
    

Detailed description: 
      SUMMARY OF STUDY PLAN

      The proposed clinical study is a Phase II, randomized, double-blinded, placebo-controlled
      trial in adults 65-85 years of age with no evidence of cognitive impairment. A total of 120
      persons will be randomized to the study, with the goal of completing 100 evaluable subjects.

      At the screening assessment, participants will complete the informed consent; questionnaires
      on basic demographic information including personal medical history and allergies to drug
      compounds; a mental ability test called the Mini-Mental Status Examination (MMSE); the SF-12
      Health survey; the Centers for Epidemiologic Studies Depression Scale (CES-D) and distribute
      instructions and forms for diet survey and gastrointestinal questionnaires.

      At the baseline/randomization assessment, study staff will (a) Confirm eligibility based on
      screening tests; (b) collect completed diet and gastrointestinal questionnaire survey forms;
      (c) collect blood for CBC/CMP and antioxidant biomarkers; (d) battery of cognitive tests
      including Rey Auditory Verbal Learning Test, Educational Testing Service - Identical Pictures
      Test, Educational Testing Service - Number Comparison Test, Educational Testing Service -
      Vocabulary Test, Trailmaking A & B, Wechsler Adult Intelligence Scale - Digit Symbol Test,
      Wechsler Intelligence Scale - Digit Span, Letter Fluency, Category Fluency. Subjects will be
      equally randomized (n=60 per arm) to blinded treatment with either NT-020 (Natura
      Therapeutics Nutrastem) or matching placebo, and an initial supply of study drug will be
      dispensed. Participants will be supplied with one-month supply of blinded treatment
      (n=60/arm) and be given the study agent intake and symptom log form. The planned intervention
      period is 2 months.

      At specified intervals (weeks 1, 3, 5, 7), participants will be contacted to inquire about
      the correct administration of the supplement or placebo as well as to assess for any adverse
      events.

      At one month (midpoint), participants will return to campus to (a) collect blood for CBC/CMP
      and antioxidant biomarkers, (b) collect unused nutritional supplement or placebo and
      completed study agent intake and symptom log form; (c) collect completed diet survey; (d)
      supply participant with new one-month supply of nutritional supplement or placebo and new
      study agent intake and symptom log form.

      At the end of the intervention (2 months), we will (a) collect blood for CBC/CMP and
      antioxidant biomarkers; (b) collect unused nutritional supplement or placebo and completed
      study agent intake and symptom log form; (c) collect completed diet survey; (d) battery of
      cognitive tests including Rey Auditory Verbal Learning Test, Educational Testing Service -
      Identical Pictures Test, Educational Testing Service - Number Comparison Test, Educational
      Testing Service - Vocabulary Test, Trailmaking A & B, Wechsler Adult Intelligence Scale -
      Digit Symbol Test, Wechsler Intelligence Scale - Digit Span, Letter Fluency, Category
      Fluency; ; (e) complete eyeblink conditioning paradigm; (f) complete timed interval tapping
      paradigm; and (g) Memory Abilities Questionnaire (MAQ-SR);

      The primary endpoint of the study is a comparison of the delay eyeblink acquisition
      performance between persons in the placebo and intervention arms. Other endpoints include:
      assessing the safety of NT-020 under the proposed dosing regimen; investigating the effect of
      NT-020 on additional measures of cognitive performance. An additional exploratory endpoints
      is to examine results from serum and urine diagnostic markers (C-reactive protein, IL-1B,
      TNFa) after 2 months of intervention with nutritional supplement vs. placebo.

      STATISTICAL CONSIDERATIONS

      Study Design/Endpoints

      The central hypothesis for this Phase II clinical trial is that adults who receive NT-020
      will exhibited faster acquisition of the delay eyeblink conditioning, as compared to adults
      on the placebo.

      Sample Size/Accrual Rate We anticipate screening 120 persons, randomizing 100, and having 88
      persons complete the two-month study period. We powered the analysis for the repeated
      measures ANOVA for the eyeblink conditioning paradigm. Power was estimated to be .80 (α =
      .05), assuming six blocks of trials during the acquisition of the CR, an effect size of f =
      .16 for the group X trials interaction, and a sample size of 44 per group, assuming an
      attrition rate of 12% over the two month period.

      Randomization and Stratification During the baseline/randomization visit, subjects will be
      randomized using the stratified randomization method prior to intervention by utilizing a
      web-based randomization system.

      Primary Endpoints The primary efficacy endpoint is to compare the acquisition of delay
      eyeblink conditioning between persons treated with NT-020 vs. placebo. The planned
      intervention period is two months. Eyeblink conditioning outcomes will be examined using a 2
      (group; NT-020, placebo) X 6 (trial) repeated measures ANOVA to examine differences in the
      acquisition of the conditioned response from the eyeblink conditioning.

      Secondary Endpoint(s) Is the facilitation of the acquisition of the delay and trace human
      eyeblink response in the nutritional supplementation group mediated by changes in
      anti-oxidant markers? In order to examine the mediation of the intervention group effects on
      eyeblink acquisition, we will adopt Baron and Kenny's approach to regression-based
      statistical mediation. In this model, there are several requirements that must be satisfied
      in order to claim statistical mediation. We will examine whether intervention group is
      associated with eyeblink acquisition, whether intervention group is associated with changes
      in biomarkers, as well as the critical step of whether the influence of intervention group on
      eyeblink acquisition is reduced or made not statistically significant by the inclusion of
      changes to biomarker values in the regression analysis.

      Evaluate the effect of NT-020 treatment on changes in paper and pencil measures of cognitive
      performance: A 2 (time; baseline, two-months) X 2 (group; NT-020, placebo) ANOVA will be
      computed on each of the cognitive test scores. The presence of a group X time interaction
      will suggest that the two groups exhibit differential change across the two time points.
    

Intervention name(s): NT-020; Placebo
Intervention type(s): Drug; Dietary Supplement
Intervention description(s): Recommended intake of NT-020 (NutraStem®) is two (2) capsules daily. This comprises Vitamin D3 (2000 IU), BioVin® (40 mg) and the proprietary blend (900mg). This recommended intake was calculated from doses analyzed in scientific research and based on the dose within the submitted patent.
Scientific description of the ingredients of the product per a 2 capsule dose Vitamin D3 (as cholecalciferol) - 2000 IU BioVin® Grape Extract - 40 mg Proprietary Blend - 900mg Green Tea Extract (Camellia sinensis) Wild Blueberries* (whole fruit) Carnosine VitaBlue® Wild Blueberry Extract*
Vaccinium angustifolium
Other Ingredients:
Magnesium stearate, Cellulose (vegetarian capsules) Contains no yeast, wheat, corn, milk, egg, soy, glutens, artificial colors or flavors, added sugar, starch or preservatives.
Other intervention name(s): Naturatherapeutics Nutrastem; Participants were to take two placebo pills, one in the morning and one at dinner.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: memory; cognition; dietary supplements