Evaluation of Soy-protein Russian Tarragon (Artemisia Dracunculus L.)
Condition: Diabetes Prevention
Study type: Interventional
Phase: Phase 1

Summary: 
      Safety and tolerability of a soy-protein Russian Tarragon complex versus a placebo.
    

Detailed description: 
      Plants from the genus Artemisia, and specifically Artemisia dracunculus L. (Russian tarragon)
      have had a long history of medicinal (health) and culinary (food) use and have been reported
      as effective as a traditional treatments for diabetes in various parts of the world. The
      overall objective of this study is to conduct early human investigation and to evaluate the
      effect of nutritional supplementation with a well characterized extract of Artemisia
      dracunculus L. The primary objectives would be to evaluate safety, tolerability and effective
      dose in non-diabetic human subjects. Secondary objectives would assess metabolism of the
      extract and evaluate effects on proposed mechanisms such as insulin secretion, lipid levels
      and/or insulin resistance.

      Single Oral Dose Evaluation

      After completing a screening visit and meeting qualifications for the single oral dose
      evaluation, subjects will receive three single doses (two different doses of the supplement
      and one dose of placebo) on three separate test periods which are separated by a washout
      period of at least 7 days. Each testing period requires an overnight stay on the inpatient
      unit. The inpatient stay will be approximately 26 hours. The doses that will be used in the
      study are 0.3, 1, 3, 10, 20 and 30 grams plus the placebo. The supplement and the placebo
      will be mixed with sugar-free flavoring in water. There will be an opportunity to sample the
      liquid drink during the screening visit.

      Screening Visit 1 (about 1 hour) - Fasting (Nothing to eat or drink other than water for at
      least 10 hours prior to appointment)

        -  Sign informed consent if willing to participate

        -  Body weight and height will be measured (body mass index will be calculated from these
           measures)

        -  Blood pressure, pulse and temperature will be measured

        -  Physical exam and ECG (electrocardiogram)

        -  Report any medications taken over the past 3 months

        -  Blood draw (about 2 teaspoons) to assess overall health

        -  Taste test

      ALL PROCEDURES AND VISITS LISTED BELOW WILL BE REPEATED 3 TIMES. ALL TESTING WILL BE DONE FOR
      EACH SINGLE DOSE TESTING PERIOD (1,2,3)

        -  Testing Period 1: Day -3, Day 1, Day 2

        -  7 Day Washout

        -  Testing Period 2: Day -3, Day 1, Day 2

        -  7 Day Washout

        -  Testing Period 3: Day -3, Day 1, Day 2

      Day -3 (about 4 hours) Fasting (Nothing to eat or drink other than water for at least 10
      hours prior to appointment)

        -  Blood pressure, pulse and temperature will be measured

        -  An IV line will be placed in an arm vein for blood draw purposes and will remain there
           throughout the testing.

        -  A blood draw (approximately 2 teaspoons) will be done before and after dosing to assess
           any changes in glucose or insulin.

        -  An Oral Glucose Tolerance Test (OGTT) will be done A blood sample will be drawn from the
           IV line, and then the subject will drink a sugar solution consisting of 75 grams of
           glucose. Blood will be drawn at specific times after the drink is consumed. Each blood
           sample will be about 1 tablespoon. (6 tablespoons total for the test). During the IV
           procedure, a small amount of the subject's own blood (less than 1 teaspoon) will
           immediately be returned into the vein through the IV after each specimen is collected.

        -  Adverse events and changes in medication will be assessed by the staff

        -  Meet with staff briefly about dietary intake and weight maintenance diets

      Day 1 (Inpatient Stay- 26 hours) Fasting (Nothing to eat or drink other than water for at
      least 10 hours prior to appointment)

        -  Admission to the inpatient unit in the morning of the Day 1 visit. The subject will
           remain on the unit overnight and be discharged on Day 2.

        -  Blood pressure, pulse and temperature will be measured.

        -  Randomization to the study dosing scheme will occur. Randomization is like flipping a
           coin. The subject and the study staff will not know what dose the subject is receiving
           or if the subject is receiving a placebo (inactive drink).

        -  Single dose of extract given (either the supplement or placebo). The dose will be given
           2 hours prior to the start of the OGTT. The extract will be in a powder form and will be
           mixed with up to 8 ounces of liquid for the subject to drink.

        -  An IV line will be placed in the arm vein for blood draw purposes and will remain there
           throughout the testing.

        -  OGTT as described above (at day -3).

        -  A blood draw (approximately 2 teaspoons) before and after dosing will be done to assess
           any changes in glucose or insulin. Blood draws will occur at 30, 60, 90, 120, 180, 240
           minutes and 12 hours after dosing.

        -  An ECG will be performed.

        -  Adverse events and changes in medication will be assessed by the staff.

        -  The subject will be asked to fast overnight until your blood work on Day 2.

      Day 2 (Inpatient) Blood pressure, weight, pulse and temperature will be measured.

        -  A physical exam will be done

        -  A 24 hour post dose blood draw (approximately 1 teaspoon) will be done.

        -  Study staff will schedule the next testing period if applicable and then the subject
           will be discharged from the inpatient unit.

      Multiple Oral Dose Evaluation

      After completing a screening visit and meeting qualifications for the multiple oral dose
      evaluation, subjects will receive three doses (two different doses of the supplement and one
      dose of placebo) over three separate 21-day test periods that are each separated by a washout
      period of at least 7 days. Each testing period involves 8 clinic visits. The doses that will
      be used in the study are 0.3, 1, and 30 grams plus the placebo. The supplement and the
      placebo will be mixed with sugar-free flavoring in water. There will be an opportunity to
      sample the liquid drink during the screening visit.

      Screening Visit 1 (about 1 hour) - Fasting (Nothing to eat or drink other than water for at
      least 10 hours prior to appointment)

        -  Sign informed consent if willing to participate

        -  Body weight and height will be measured (body mass index will be calculated from these
           measures)

        -  Blood pressure, pulse and temperature will be measured

        -  Physical exam and ECG (electrocardiogram)

        -  Report any medications taken over the past 3 months

        -  Blood draw (about 2 teaspoons) and urine collection to assess overall health

        -  Meet with dietitian about normal dietary intake

        -  Taste test

      ALL PROCEDURES AND VISITS LISTED BELOW WILL BE REPEATED 3 TIMES. ALL TESTING WILL BE DONE FOR
      EACH MULTIPLE DOSE TESTING PERIOD (1,2,3)

        -  Testing Period 1: Day -3, Day 1, Day 3, Day 7, Day 10, Day 14, Day 17, Day 21

        -  7 Day Washout

        -  Testing Period 2: Day -3, Day 1, Day 3, Day 7, Day 10, Day 14, Day 17, Day 21

        -  7 Day Washout

        -  Testing Period 3: Day -3, Day 1, Day 3, Day 7, Day 10, Day 14, Day 17, Day 21

      Day -3 (about 4 hours) Fasting (Nothing to eat or drink other than water for at least 10
      hours prior to appointment)

        -  Blood pressure, pulse, weight, and temperature will be measured

        -  An IV line will be placed in an arm vein for blood draw purposes and will remain there
           throughout the testing.

        -  An Oral Glucose Tolerance Test (OGTT) will be done. A blood sample will be drawn from
           the IV line, and then the subject will drink a sugar solution consisting of 75 grams of
           glucose. Blood will be drawn at specific times after the drink is consumed. Each blood
           sample will be about 1 tablespoon (3 tablespoons total for the test). During the IV
           procedure, a small amount of the subject's own blood (less than 1 teaspoon) will
           immediately be returned into the vein through the IV after each specimen is collected.

        -  Females of child-bearing potential will have a urine pregnancy test

        -  A dual-energy X-ray absorptiometry (DXA) scan will be performed using a whole-body
           scanner. This scan measures the amount of bone, muscle, and fat in the body. The subject
           will wear a hospital gown, remove all metal-containing objects, and lie down on a table
           with legs held together by Velcro straps. A scanner emitting low-energy X rays and a
           detector will pass along the body. The subject is asked to remain completely still for
           the duration of the 10-minute scan.

        -  Adverse events and changes in medication will be assessed by the staff

        -  Meet with staff to assess dietary intake since prior visit

      Day 1 (about 45 minutes) Non-fasting

        -  Blood pressure, pulse, weight, and temperature will be measured.

        -  Randomization to the study dosing scheme will occur. Randomization is like flipping a
           coin. The subject and the study staff will not know what dose the subject is receiving
           or if the subject is receiving a placebo (inactive drink).

        -  The first dose of extract will be given (either the supplement or placebo). The subject
           will be given instructions on how to take the extract at home. The extract will be in a
           powder form to be mixed with up to 8 ounces of liquid to drink.

        -  Adverse events and changes in medication will be assessed by the staff.

      Days 3, 10, and 17 (about 30 minutes each) Non-fasting

        -  Blood pressure, pulse, weight, and temperature will be measured.

        -  Compliance with extract dosing will be assessed and additional extract dispensed as
           needed.

        -  Adverse events and changes in medication will be assessed by the staff.

      Days 7, 14, and 21 (about 6 hours each) Fasting (Nothing to eat or drink other than water for
      at least 10 hours prior to appointment)

        -  Blood pressure, pulse, weight, and temperature will be measured.

        -  Compliance with extract dosing will be assessed and additional extract dispensed as
           needed (except at Day 21 when dosage is stopped).

        -  Adverse events and changes in medication will be assessed by the staff.

        -  Physical exam and ECG (electrocardiogram) will be performed.

        -  An IV line will be placed in the arm vein for blood draw purposes and will remain there
           throughout the testing.

        -  OGTT as described above (at Day -3).

        -  A blood draw (approximately 3 tablespoons) before and after dosing will be done to
           assess any changes in glucose or insulin. Blood draws will occur at 0, 30, 60, 90, 120,
           180, and 240 minutes after dosing.

        -  Urine samples will be collected throughout the test day to measure the body's response
           to the daily doses of extract.

        -  Meet with dietitian to assess food intake to assure it has not changed from normal diet.

        -  At Day 21 only, a DXA scan will be performed as described above (at Day -3). Females of
           child-bearing potential will have a urine pregnancy test prior to the DXA scan.
    

Intervention name(s): Dose 1; Dose 2; Dose 0; Dose 3; Dose 4; Dose 5; Dose 6
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement; Dietary Supplement; Dietary Supplement; Dietary Supplement; Dietary Supplement
Intervention description(s): Russian Tarragon Nutrasorb 0.3 g; Russian Tarragon Nutrasorb 1 g; Placebo; Russian Tarragon Nutrasorb 3 g; Russian Tarragon Nutrasorb 10 g; Russian Tarragon Nutrasorb 20 g; Russian Tarragon Nutrasorb 30 g
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention