A Randomized, Controlled, Crossover Study to Assess the Glucose and Insulin Excursions of a Test Fiber
Condition: Healthy
Study type: Interventional

Summary: 
      The objective of this trial is to evaluate the postprandial glucose and insulin responses to
      replacing digestible carbohydrates with resistant starch type 4 (RS4) in a baked product in
      healthy men and women. A randomized, double-blinded cross-over study will be conducted
      comparing two foods (a reference food and a test food). The primary outcome variable will be
      the incremental area under the curve (iAUC) for capillary glucose from pre-product
      consumption (average of t = -15 and -5 min) to 120 min (iAUC0-120 min). This study will
      provide substantiation for a beneficial reduction in glycemic response followed by the
      consumption of the active product containing an efficacious dose of resistant starch type 4
      (RS4).
    

Detailed description: 
      The study is a randomized, controlled, double-blind, crossover trial that includes one
      screening visit (Visit 1; day -7) and two test visits (Visits 2 and 3; days 0 and 7) which
      are separated by a washout period of 4-7 days. At Visit 1 (day -7), subjects will provide
      informed consent and undergo screening assessments including evaluations of medical history,
      prior/current medication/supplement use, inclusion and exclusion criteria, height, body
      weight, BMI, vital signs, and Vein Access Scale. A fasting capillary blood glucose will be
      assessed for eligibility purposes and an in-clinic urine pregnancy test (all women) will also
      be obtained. Subjects will then be dispensed a 24-h Diet Record with instructions to record
      intake the day prior to Visit 2 (day 0). At Visit 2 (day 0), subjects will arrive at the
      clinic fasted (10-14 h, water only, anchored to the t = -15 min blood draw), to undergo
      clinic visit procedures. Adverse events (AE) will be assessed and subjects will be queried
      about test day instructions compliance. Additionally, the 24-h Diet Record will be collected
      and reviewed. Eligible subjects will be randomly assigned to a randomization sequence and
      will undergo the glycemic and insulinemic response test with blood glucose concentrations
      assessed via capillary measurement and insulin concentrations assessed via venous
      measurement. Blood samples (capillary and venous) will be obtained at t = -15 and -5 ± 5 min.
      Subjects will consume the study product in its entirety within 10 min at t = 0 min with 8 oz
      of water. Capillary and venous blood samples will be obtained at t = 15, 30, 45, 60, 90, and
      120 ± 5 min, where t = 0 min is the start of study product consumption, to assess glucose and
      insulin concentrations. Subjects will be provided one-8 oz bottle of water to consume at t =
      0 to 60 min and one-8 oz bottle of water to consume at t = 61 to 120 min. Water consumption
      will be recorded and replicated at the subsequent test visits. AEs will be assessed and
      subjects will be dispensed a blank/new 24-h Diet Record to record all food and beverage
      consumed the day prior to Visit 3, day 7; as well as a copy of the completed 24-h Diet Record
      (from day -1) with instructions to replicate the same food and beverage intake as closely as
      possible the day prior to the next test visit (Visit 3, day 7). Test day instructions will
      also be provided. At Visit 3 (day 7), subjects will return to the clinic for clinic visit
      procedures. AEs will be assessed and subjects will be queried about test day instructions
      compliance. The 24-h Diet Record will be collected and study staff will review the 24-h Diet
      Record to compare food and beverage consumption to the day -1 Diet Record for consistency.
      Subjects will then crossover to the next study product in their test sequence and repeat the
      glycemic/insulinemic response test described above for Visit 2. At the conclusion of the
      glycemic/insulinemic response test, AEs will be assessed.

      An evaluable sample size of 19 is required to observe a statistically significant difference
      between active and control products (α = 0.05 (2- tailed); power = 80%) assuming that the
      glucose response of the Cargill active product is 61% of that of the control product and
      standard deviation is 65% of the mean value (standard deviation estimation is based on a
      recently completed proprietary study conducted by Biofortis on baked products containing
      different amounts of fiber). To account for possible attrition, a total of 22 subjects will
      be enrolled. Each subject will consume a single serving of the control or active product.
      These consumption events will be separated by at least 4 days.

      All statistical analyses will be conducted using Statistical Analysis Systems (SAS) for
      Windows (version 9.4, Cary, NC) and/or R 3.3.1 (R Core Team 2016). The data will be analyzed
      for the modified intent-to-treat population, which will include all subjects who complete the
      test condition and the reference product. Assessment for outliers, as per the International
      Organization for Standardization (ISO) standards, will also be conducted. All decisions
      regarding subject population and data inclusion will be documented prior to database lock.
      Descriptive statistics [number of subjects, mean, standard deviation, standard error of the
      mean (SEM), median, interquartile limits, minimum and maximum or frequency counts] will be
      presented for subject demographics and anthropometric measurements collected at
      screening/baseline. Incremental area under the curve (iAUC) 0-120 min will be calculated as
      outlined in ISO 26642:2010(E) for each subject. Descriptive statistics (i.e. number of
      subjects, minimum and maximum, median, inter-quartile limits, mean, SEM, and standard
      deviation) will be presented for all the continuous outcomes for each test group. All tests
      of significance, unless otherwise stated, will be performed at alpha=0.05, two sided. A
      repeated measures analysis of covariance (ANCOVA) will be used to assess differences between
      test groups for the primary and secondary outcome variables with the exception of the
      comparisons between groups for glucose and insulin concentrations at each time point. Initial
      repeated measures ANCOVA models will contain terms for test group, test sequence, and test
      period, with test group specified as a repeated effect and subject nested within sequence.
      Models will be reduced using a backward selection method until only significant terms or test
      group remains in the model. Appropriate least squares mean values and corresponding SEM will
      be derived from the final model for each test group. Assumption of normality of residuals
      will be investigated at the 5% level with the Shapiro-Wilk test (Shapiro 1965). If the
      normality assumption is not satisfied, then an analysis based on ranks will be performed.
      Average blood glucose response curve, as described in ISO 26642:2010(E), and time curve plots
      of the observed glucose and insulin concentration per time point per test product will be
      presented. Glucose concentrations will be provided in mg/dL and insulin concentrations will
      be provided at μIU/mL.
    

Intervention name(s): Control digestible carbohydrate; Test resistant starch type 4
Intervention type(s): Other; Other
Intervention description(s): Single serving of control product; Single serving of test product
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Randomized, controlled, double-blind, crossover trial that includes one screening visit and two test visits separated by a washout period of 4-7 days. At Visit 1 (day -7), subjects will provide informed consent and undergo screening assessments. Test day instructions will also be provided.
At Visit 2 (day 0), subjects will arrive at the clinic fasted (10-14 h, water only, anchored to the t = -15 min blood draw), to undergo clinic visit procedures. Eligible subjects will be randomly assigned to a randomization sequence and will undergo the glycemic and insulinemic response test with blood glucose concentrations assessed via capillary measurement and insulin concentrations assessed via venous measurement.
At Visit 3 (day 7), subjects will return to the clinic for clinic visit procedures. Subjects will then crossover to the next study product in their test sequence and repeat the glycemic/insulinemic response test described above for Visit 2.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Other
Keywords: Fiber; Postprandial glucose; Insulin; Resistant Starch Type 4