<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02988999</url>
  </required_header>
  <id_info>
    <org_study_id>CMU-D-allulose02</org_study_id>
    <nct_id>NCT02988999</nct_id>
  </id_info>
  <brief_title>Efficacy of D-allulose on Weight and Fat Loss and Insulin Resistance in Non-diabetic Obese Subjects</brief_title>
  <official_title>The Efficacy of D-allulose (Psicose) on Weight and Fat Loss and Insulin Resistance by a Randomized Double-blind, Parallel-group Study in Non-diabetic Obese Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chiang Mai University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Kagawa University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Chiang Mai University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Prospective, randomized, double-blind, controlled-trial 30 subjects in each groups Group - I&#xD;
      consume pure D-allulose 5 g 3 times a day before meal to right after meal (with any liquid)&#xD;
      and Group - II control group with non-calorie sweetener erythritol 5 g 3 times a day before&#xD;
      meal to right after meal (with any liquid) Total number: n = 60 Either males or females,&#xD;
      non-diabetic, aged &gt; 18 years old with BMI ≥ 25 kg/m2&#xD;
&#xD;
      Primary objectives Efficacy&#xD;
&#xD;
      1. Compare the efficacy of pure D-allulose (psicose) plus conventional therapy on 1.1&#xD;
      visceral fat area (VFA), subcutaneous fat area (SFA), total fat area (TFA) change 1.2 body&#xD;
      weight, BMI and body fat percentage (with impedance method) change after 24 weeks of&#xD;
      D-allulose (psicose) consumption to erythritol consumption and between pre- and&#xD;
      post-intervention.&#xD;
&#xD;
      Secondary objectives 1. Efficacy of pure D-allulose (psicose) plus conventional therapy&#xD;
      versus erythritol plus conventional therapy on 1.1 insulin resistance, fasting plasma&#xD;
      glucose, HbA1c 1.2 adiponectin, leptin and tumor necrosis factor-alpha, lipid profiles (total&#xD;
      cholesterol, HDL-C, LDL-C, triglyceride, very low-density lipoprotein, LDL, chylomicron),&#xD;
      apolipoprotein AI, apolipoprotein AII,apolipoprotein B48, apolipoprotein CIII and&#xD;
      apolipoprotein E, free fatty acids 1.4 waist circumference, hip circumference, waist/hip&#xD;
      ratio&#xD;
&#xD;
      Safety&#xD;
&#xD;
      1. Safety of the study by comparing with conventional therapy, monitoring blood pressure,&#xD;
      pulse rate, hematological parameters and urinalysis&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Subjects and methods Study product The test product is the pure D-allulose which is a rare&#xD;
      sugar. The control product is the non-calorie sweetener erythritol.&#xD;
&#xD;
      Study design This is a single center, prospective, randomized, control trial. After informed&#xD;
      consent is obtained, history taking and physical examination will be performed to ensure that&#xD;
      the patients met all inclusion criteria and had no exclusion criteria.&#xD;
&#xD;
      At the screening day, venous blood samples will be collected following an overnight fasting&#xD;
      of at least 8 hours. Complete blood count (CBC), chemistry including fasting plasma glucose&#xD;
      (FPG), glycated hemoglobin (HbA1c), insulin, blood urea nitrogen (BUN), creatinine, lipid&#xD;
      profiles (total cholesterol, HDL-C, LDL-C, triglyceride, very low-density lipoprotein), blood&#xD;
      urea nitrogen, creatinine, total protein, Albumin, albumin/globulin ratio, glutamine&#xD;
      oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) , Gamma-glutamyl&#xD;
      transpeptidase (GGT), lactate dehydrogenase (LDH), total bilirubin (including Direct and&#xD;
      Indirect), alkaline phosphatase, uric acid, plasma amylase, cholinesterase, Sodium, Chloride,&#xD;
      potassium, carbon dioxide , Calcium, inorganic phosphate, magnesium, plasma iron will be&#xD;
      measured.&#xD;
&#xD;
      Urine will be collected for urinalysis and urine pregnancy test will be performed to exclude&#xD;
      pregnant women from the study.&#xD;
&#xD;
      Visceral fat area (VFA), subcutaneous fat area (SFA), total fat area (TFA) will be measured&#xD;
      with abdominal CT scan at umbilical level (L4) and bioelectrical impedance at D-7 or&#xD;
      screening visit.&#xD;
&#xD;
      The eligible subjects will be randomized with an equal probability of receiving either pure&#xD;
      D-allulose 5 g 3 times a day from 30 min before meal to right after meals (with any liquid)&#xD;
      plus conventional therapy or placebo (non-calorie sweetener erythritol) 5 g 3 times a day&#xD;
      from 30 min before meal to right after meal (with any liquid) plus conventional therapy for&#xD;
      24 weeks. Both the subjects and the investigator will be blinded to the type of the product.&#xD;
      Subjects in both groups will be instructed to modify their lifestyle to control their diet to&#xD;
      1200 kcal for women and 1500 kcal for men and increase physical activity.&#xD;
&#xD;
      Subjects will be asked to do 3-d food record per week (2 working days and 1 weekend) entire&#xD;
      of the study. Subjects will need to record any exercise they do including type and duration&#xD;
      during in the study. Subjects will be asked to visit every 4 weeks for follow-up for totally&#xD;
      9 visits including screening day or D -7, D0, end of week 4, 8, 12, 16, 20, 24 and 4 weeks&#xD;
      post intervention (at the end of week 28) in 29 weeks duration.&#xD;
&#xD;
      Assessment of insulin resistance index (IRI) was calculated from the homeostasis model&#xD;
      assessment of insulin resistance (HOMA-IR) using FPG (mmol/L) multiply by fasting insulin&#xD;
      (U/ml) divided with 22.5.&#xD;
&#xD;
      The satisfaction of the product will be asked at 4 weeks, 12 weeks and 24 weeks after&#xD;
      consumption of the study products.&#xD;
&#xD;
      From the visit 1 to visit 8, same blood samples as the screening will be measured.&#xD;
&#xD;
      At the screening visit, visit 4 and visit 7, CT abdomen measurements will be conducted.&#xD;
&#xD;
      At the visit 1 and visit 7, adiponectin, leptin, tumor necrosis factor -alpha will be&#xD;
      measured.&#xD;
&#xD;
      At the visit 1, visit 4, visit 7 and visit 8, other lipid profiles will be measured including&#xD;
      very low-density lipoprotein and Chylomicron fractionation , Apolipoprotein (AI, AII，C-III,&#xD;
      E), Apolipoprotein (B48, B100), nonesterified fatty acid&#xD;
&#xD;
      Adverse Event Assessment At each visit, subjects will be asked an open question as if he/she&#xD;
      has experienced any abnormal symptoms. Any symptom reported by the subject will be recorded&#xD;
      as an adverse events with details of the event, its severity, start and stop dates, and&#xD;
      relationship to study products.&#xD;
&#xD;
      Withdrawal criteria&#xD;
&#xD;
        1. Consume study product less than 90% during treatment period&#xD;
&#xD;
        2. Start taking any medication that may affect body weight during in the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>September 2016</start_date>
  <completion_date type="Anticipated">November 2017</completion_date>
  <primary_completion_date type="Anticipated">August 2017</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Body composition change after 24 weeks of D-allulose consumption to erythritol consumption</measure>
    <time_frame>28 weeks (assess 4 weeks after 24 weeks consumption of the study product)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Body weight change after 24 weeks of D-allulose consumption to erythritol consumption</measure>
    <time_frame>28 weeks (assess 4 weeks after 24 weeks consumption of the study product)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>BMI change after 24 weeks of D-allulose consumption to erythritol consumption</measure>
    <time_frame>28 weeks (assess 4 weeks after 24 weeks consumption of the study product)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Body fat percentage change after 24 weeks of D-allulose consumption to erythritol consumption</measure>
    <time_frame>28 weeks (assess 4 weeks after 24 weeks consumption of the study product)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>insulin resistance change (as calculated from HOMA-IR) after 24 weeks of D-allulose consumption to erythritol consumption</measure>
    <time_frame>28 weeks (assess 4 weeks after 24 weeks consumption of the study product)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fasting plasma glucose change after 24 weeks of D-allulose consumption to erythritol consumption</measure>
    <time_frame>28 weeks (assess 4 weeks after 24 weeks consumption of the study product)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HbA1c change after 24 weeks of D-allulose consumption to erythritol consumption</measure>
    <time_frame>28 weeks (assess 4 weeks after 24 weeks consumption of the study product)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in inflammatory markers (adiponectin, leptin and tumor necrosis factor-alpha) after 24 weeks of D-allulose consumption to erythritol consumption</measure>
    <time_frame>28 weeks (assess 4 weeks after 24 weeks consumption of the study product)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in lipid profiles</measure>
    <time_frame>28 weeks (assess 4 weeks after 24 weeks consumption of the study product)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes on waist circumference, hip circumference</measure>
    <time_frame>28 weeks (assess 4 weeks after 24 weeks consumption of the study product)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes on waist/ hip ratio</measure>
    <time_frame>28 weeks (assess 4 weeks after 24 weeks consumption of the study product)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events by monitoring clinical and laboratory data</measure>
    <time_frame>28 weeks (assess 4 weeks after 24 weeks consumption of the study product)</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Obesity</condition>
  <arm_group>
    <arm_group_label>D-allulose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>D-allulose 5 gm 3 times a day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>erythritol</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>erythritol 5 gm 3 times a day</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>D-allulose</intervention_name>
    <description>D-allulose (psicose), a C-3 epimer of D-fructose, is defined one of the rare sugars since it is rarely found in nature. Rare sugars are monosaccharides which present in small quantities in commercial mixtures of D-glucose and D-fructose obtained from hydrolysis of sucrose or isomerization of D-glucose (5). D-allulose (psicose) has been demonstrated to be a non-calorie monosaccharide which has approximately 70% sweetness of sucrose. Various physiological activities of D-allulose (psicose) have been revealed. Of those, its glucose suppressive effect has been proven by both animal and clinical studies.</description>
    <arm_group_label>D-allulose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>erythritol</intervention_name>
    <description>non-calorie sweetener</description>
    <arm_group_label>erythritol</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female, age &gt; 18 years and legal age of consent.&#xD;
&#xD;
          2. If female, the subject is either post-menopausal or surgically sterilized, or has a&#xD;
             negative urine pregnancy test within 7 days prior to enrollment and will use adequate&#xD;
             contraception during the study.&#xD;
&#xD;
          3. Obesity, defined as BMI ≥ 25 kg/m2&#xD;
&#xD;
          4. Stable weight (weight change no more than 5% within 3 months)&#xD;
&#xD;
          5. If subject has been treated with medications that might cause weight change (such as&#xD;
             corticosteroid, antidepressant, antipsychotics, oral contraceptive pills) prior to&#xD;
             admission, he/she must have taken the medication regularly at a steady dose for at&#xD;
             least 8 weeks up.&#xD;
&#xD;
          6. The subject has provided written informed consent prior to admission to the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        A subject will be excluded from the study for any of the following reasons:&#xD;
&#xD;
          1. Pregnancy or lactation&#xD;
&#xD;
          2. Diagnosed with diabetes mellitus&#xD;
&#xD;
          3. Weight change ≥ 5 % within 3 months prior to admission to the study&#xD;
&#xD;
          4. Has taken any weight loss medications within 3 months prior to admission to the study&#xD;
&#xD;
          5. Immunocompromised status, including a debilitated state or malignancy&#xD;
&#xD;
          6. Active liver, renal, thyroid diseases&#xD;
&#xD;
          7. Frequent alcoholic consumption more than twice a week; with beer &gt; 360 mL, alcohol &gt;&#xD;
             45 mL, wine &gt; 150 mL for female, or beer &gt; 720 mL, whisky &gt; 90 mL, wine &gt; 300 mL for&#xD;
             male each time&#xD;
&#xD;
          8. Has gastrointestinal symptoms such as nausea, vomiting, loss of appetite, premature&#xD;
             satiety, diarrhea, or chronic constipation&#xD;
&#xD;
          9. Lack of ability or willingness to give informed consent&#xD;
&#xD;
         10. Taken any medications than might cause weight loss or weight gain such as&#xD;
             corticosteroid, antidepressant, antipsychotics, oral contraceptive pills &lt; 8 weeks or&#xD;
             change the dose of these medication with 8 week prior to admission&#xD;
&#xD;
         11. Enrolled in any other clinical study within 3 months before enrolment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Supawan Buranapin, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Chiang Mai University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Supawan Buranapin, MD</last_name>
    <phone>66-867310392</phone>
    <email>supawan.b@cmu.ac.th</email>
  </overall_contact>
  <location>
    <facility>
      <name>Faculty of Medicine, Chiang Mai University</name>
      <address>
        <city>Muang Chiang Mai</city>
        <state>Chiang Mai</state>
        <zip>50200</zip>
        <country>Thailand</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Supawan Buranapin, MD</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Thailand</country>
  </location_countries>
  <reference>
    <citation>Cree GM, Perlin AS. O-isopropylidene derivatives of D-allulose (D-psicose) and D-erythro-hexopyranos-2,3-diulose. Can J Biochem. 1968 Aug;46(8):765-70. doi: 10.1139/o68-117. No abstract available.</citation>
    <PMID>4299740</PMID>
  </reference>
  <reference>
    <citation>Takeshita K, Suga A, Takada G, Izumori K. Mass production of D-psicose from d-fructose by a continuous bioreactor system using immobilized D-tagatose 3-epimerase. J Biosci Bioeng. 2000;90(4):453-5. doi: 10.1016/s1389-1723(01)80018-9.</citation>
    <PMID>16232889</PMID>
  </reference>
  <reference>
    <citation>Granstrom TB, Takata G, Tokuda M, Izumori K. Izumoring: a novel and complete strategy for bioproduction of rare sugars. J Biosci Bioeng. 2004;97(2):89-94. doi: 10.1016/S1389-1723(04)70173-5.</citation>
    <PMID>16233597</PMID>
  </reference>
  <reference>
    <citation>Matsuo T, Suzuki H, Hashiguchi M, Izumori K. D-psicose is a rare sugar that provides no energy to growing rats. J Nutr Sci Vitaminol (Tokyo). 2002 Feb;48(1):77-80. doi: 10.3177/jnsv.48.77.</citation>
    <PMID>12026195</PMID>
  </reference>
  <reference>
    <citation>Matsuo T, Izumori K. d-Psicose Inhibits Intestinal alpha-Glucosidase and Suppresses the Glycemic Response after Ingestion of Carbohydrates in Rats. J Clin Biochem Nutr. 2009 Sep;45(2):202-6. doi: 10.3164/jcbn.09-36. Epub 2009 Aug 28.</citation>
    <PMID>19794929</PMID>
  </reference>
  <reference>
    <citation>Iida T, Kishimoto Y, Yoshikawa Y, Hayashi N, Okuma K, Tohi M, Yagi K, Matsuo T, Izumori K. Acute D-psicose administration decreases the glycemic responses to an oral maltodextrin tolerance test in normal adults. J Nutr Sci Vitaminol (Tokyo). 2008 Dec;54(6):511-4. doi: 10.3177/jnsv.54.511.</citation>
    <PMID>19155592</PMID>
  </reference>
  <reference>
    <citation>Hayashi N, Iida T, Yamada T, Okuma K, Takehara I, Yamamoto T, Yamada K, Tokuda M. Study on the postprandial blood glucose suppression effect of D-psicose in borderline diabetes and the safety of long-term ingestion by normal human subjects. Biosci Biotechnol Biochem. 2010;74(3):510-9. doi: 10.1271/bbb.90707. Epub 2010 Mar 7.</citation>
    <PMID>20208358</PMID>
  </reference>
  <reference>
    <citation>Hossain A, Yamaguchi F, Matsunaga T, Hirata Y, Kamitori K, Dong Y, Sui L, Tsukamoto I, Ueno M, Tokuda M. Rare sugar D-psicose protects pancreas beta-islets and thus improves insulin resistance in OLETF rats. Biochem Biophys Res Commun. 2012 Sep 7;425(4):717-23. doi: 10.1016/j.bbrc.2012.07.135. Epub 2012 Aug 1.</citation>
    <PMID>22877751</PMID>
  </reference>
  <reference>
    <citation>Ochiai M, Onishi K, Yamada T, Iida T, Matsuo T. D-psicose increases energy expenditure and decreases body fat accumulation in rats fed a high-sucrose diet. Int J Food Sci Nutr. 2014 Mar;65(2):245-50. doi: 10.3109/09637486.2013.845653. Epub 2013 Oct 21.</citation>
    <PMID>24144428</PMID>
  </reference>
  <reference>
    <citation>Matsuo T, Izumori K. Effects of dietary D-psicose on diurnal variation in plasma glucose and insulin concentrations of rats. Biosci Biotechnol Biochem. 2006 Sep;70(9):2081-5. doi: 10.1271/bbb.60036. Epub 2006 Sep 7.</citation>
    <PMID>16960391</PMID>
  </reference>
  <reference>
    <citation>Ochiai M, Nakanishi Y, Yamada T, Iida T, Matsuo T. Inhibition by dietary D-psicose of body fat accumulation in adult rats fed a high-sucrose diet. Biosci Biotechnol Biochem. 2013;77(5):1123-6. doi: 10.1271/bbb.130019. Epub 2013 May 7.</citation>
    <PMID>23649241</PMID>
  </reference>
  <reference>
    <citation>Chung YM, Hyun Lee J, Youl Kim D, Hwang SH, Hong YH, Kim SB, Jin Lee S, Hye Park C. Dietary D-psicose reduced visceral fat mass in high-fat diet-induced obese rats. J Food Sci. 2012 Feb;77(2):H53-8. doi: 10.1111/j.1750-3841.2011.02571.x.</citation>
    <PMID>22339545</PMID>
  </reference>
  <reference>
    <citation>Wong JM, de Souza R, Kendall CW, Emam A, Jenkins DJ. Colonic health: fermentation and short chain fatty acids. J Clin Gastroenterol. 2006 Mar;40(3):235-43. doi: 10.1097/00004836-200603000-00015.</citation>
    <PMID>16633129</PMID>
  </reference>
  <reference>
    <citation>Haslam DW, James WP. Obesity. Lancet. 2005 Oct 1;366(9492):1197-209. doi: 10.1016/S0140-6736(05)67483-1.</citation>
    <PMID>16198769</PMID>
  </reference>
  <reference>
    <citation>The Western Pacific Region, World Health Organization, International Associates for the study of obesity, International Obesity Task Force. The Asia-Pacific Perspective: redefining obesity and its treatment. Melbourne: Health Communications Australia, 2000.</citation>
  </reference>
  <reference>
    <citation>Fontaine KR, Redden DT, Wang C, Westfall AO, Allison DB. Years of life lost due to obesity. JAMA. 2003 Jan 8;289(2):187-93. doi: 10.1001/jama.289.2.187.</citation>
    <PMID>12517229</PMID>
  </reference>
  <reference>
    <citation>Johnson WD, Brashear MM, Gupta AK, Rood JC, Ryan DH. Incremental weight loss improves cardiometabolic risk in extremely obese adults. Am J Med. 2011 Oct;124(10):931-8. doi: 10.1016/j.amjmed.2011.04.033.</citation>
    <PMID>21962313</PMID>
  </reference>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>November 21, 2016</study_first_submitted>
  <study_first_submitted_qc>December 8, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 12, 2016</study_first_posted>
  <last_update_submitted>December 8, 2016</last_update_submitted>
  <last_update_submitted_qc>December 8, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 12, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Chiang Mai University</investigator_affiliation>
    <investigator_full_name>Supawan Buranapin</investigator_full_name>
    <investigator_title>Assisstant professor</investigator_title>
  </responsible_party>
  <keyword>D-allulose or erythritol</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin Resistance</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Erythritol</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02988999
org study id: CMU-D-allulose02
nct id: NCT02988999
lead sponsor: 
collaborator: 
has dmc: Yes
Prospective, randomized, double-blind, controlled-trial 30 subjects in each groups Group - I
      consume pure D-allulose 5 g 3 times a day before meal to right after meal (with any liquid)
      and Group - II control group with non-calorie sweetener erythritol 5 g 3 times a day before
      meal to right after meal (with any liquid) Total number: n = 60 Either males or females,
      non-diabetic, aged > 18 years old with BMI ≥ 25 kg/m2

      Primary objectives Efficacy

      1. Compare the efficacy of pure D-allulose (psicose) plus conventional therapy on 1.1
      visceral fat area (VFA), subcutaneous fat area (SFA), total fat area (TFA) change 1.2 body
      weight, BMI and body fat percentage (with impedance method) change after 24 weeks of
      D-allulose (psicose) consumption to erythritol consumption and between pre- and
      post-intervention.

      Secondary objectives 1. Efficacy of pure D-allulose (psicose) plus conventional therapy
      versus erythritol plus conventional therapy on 1.1 insulin resistance, fasting plasma
      glucose, HbA1c 1.2 adiponectin, leptin and tumor necrosis factor-alpha, lipid profiles (total
      cholesterol, HDL-C, LDL-C, triglyceride, very low-density lipoprotein, LDL, chylomicron),
      apolipoprotein AI, apolipoprotein AII,apolipoprotein B48, apolipoprotein CIII and
      apolipoprotein E, free fatty acids 1.4 waist circumference, hip circumference, waist/hip
      ratio

      Safety

      1. Safety of the study by comparing with conventional therapy, monitoring blood pressure,
      pulse rate, hematological parameters and urinalysis
Subjects and methods Study product The test product is the pure D-allulose which is a rare
      sugar. The control product is the non-calorie sweetener erythritol.

      Study design This is a single center, prospective, randomized, control trial. After informed
      consent is obtained, history taking and physical examination will be performed to ensure that
      the patients met all inclusion criteria and had no exclusion criteria.

      At the screening day, venous blood samples will be collected following an overnight fasting
      of at least 8 hours. Complete blood count (CBC), chemistry including fasting plasma glucose
      (FPG), glycated hemoglobin (HbA1c), insulin, blood urea nitrogen (BUN), creatinine, lipid
      profiles (total cholesterol, HDL-C, LDL-C, triglyceride, very low-density lipoprotein), blood
      urea nitrogen, creatinine, total protein, Albumin, albumin/globulin ratio, glutamine
      oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) , Gamma-glutamyl
      transpeptidase (GGT), lactate dehydrogenase (LDH), total bilirubin (including Direct and
      Indirect), alkaline phosphatase, uric acid, plasma amylase, cholinesterase, Sodium, Chloride,
      potassium, carbon dioxide , Calcium, inorganic phosphate, magnesium, plasma iron will be
      measured.

      Urine will be collected for urinalysis and urine pregnancy test will be performed to exclude
      pregnant women from the study.

      Visceral fat area (VFA), subcutaneous fat area (SFA), total fat area (TFA) will be measured
      with abdominal CT scan at umbilical level (L4) and bioelectrical impedance at D-7 or
      screening visit.

      The eligible subjects will be randomized with an equal probability of receiving either pure
      D-allulose 5 g 3 times a day from 30 min before meal to right after meals (with any liquid)
      plus conventional therapy or placebo (non-calorie sweetener erythritol) 5 g 3 times a day
      from 30 min before meal to right after meal (with any liquid) plus conventional therapy for
      24 weeks. Both the subjects and the investigator will be blinded to the type of the product.
      Subjects in both groups will be instructed to modify their lifestyle to control their diet to
      1200 kcal for women and 1500 kcal for men and increase physical activity.

      Subjects will be asked to do 3-d food record per week (2 working days and 1 weekend) entire
      of the study. Subjects will need to record any exercise they do including type and duration
      during in the study. Subjects will be asked to visit every 4 weeks for follow-up for totally
      9 visits including screening day or D -7, D0, end of week 4, 8, 12, 16, 20, 24 and 4 weeks
      post intervention (at the end of week 28) in 29 weeks duration.

      Assessment of insulin resistance index (IRI) was calculated from the homeostasis model
      assessment of insulin resistance (HOMA-IR) using FPG (mmol/L) multiply by fasting insulin
      (U/ml) divided with 22.5.

      The satisfaction of the product will be asked at 4 weeks, 12 weeks and 24 weeks after
      consumption of the study products.

      From the visit 1 to visit 8, same blood samples as the screening will be measured.

      At the screening visit, visit 4 and visit 7, CT abdomen measurements will be conducted.

      At the visit 1 and visit 7, adiponectin, leptin, tumor necrosis factor -alpha will be
      measured.

      At the visit 1, visit 4, visit 7 and visit 8, other lipid profiles will be measured including
      very low-density lipoprotein and Chylomicron fractionation , Apolipoprotein (AI, AII，C-III,
      E), Apolipoprotein (B48, B100), nonesterified fatty acid

      Adverse Event Assessment At each visit, subjects will be asked an open question as if he/she
      has experienced any abnormal symptoms. Any symptom reported by the subject will be recorded
      as an adverse events with details of the event, its severity, start and stop dates, and
      relationship to study products.

      Withdrawal criteria

        1. Consume study product less than 90% during treatment period

        2. Start taking any medication that may affect body weight during in the study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Body composition change after 24 weeks of D-allulose consumption to erythritol consumption
time frame: 28 weeks (assess 4 weeks after 24 weeks consumption of the study product)
measure: Body weight change after 24 weeks of D-allulose consumption to erythritol consumption
time frame: 28 weeks (assess 4 weeks after 24 weeks consumption of the study product)
measure: BMI change after 24 weeks of D-allulose consumption to erythritol consumption
time frame: 28 weeks (assess 4 weeks after 24 weeks consumption of the study product)
measure: Body fat percentage change after 24 weeks of D-allulose consumption to erythritol consumption
time frame: 28 weeks (assess 4 weeks after 24 weeks consumption of the study product)
measure: insulin resistance change (as calculated from HOMA-IR) after 24 weeks of D-allulose consumption to erythritol consumption
time frame: 28 weeks (assess 4 weeks after 24 weeks consumption of the study product)
measure: Fasting plasma glucose change after 24 weeks of D-allulose consumption to erythritol consumption
time frame: 28 weeks (assess 4 weeks after 24 weeks consumption of the study product)
measure: HbA1c change after 24 weeks of D-allulose consumption to erythritol consumption
time frame: 28 weeks (assess 4 weeks after 24 weeks consumption of the study product)
measure: Change in inflammatory markers (adiponectin, leptin and tumor necrosis factor-alpha) after 24 weeks of D-allulose consumption to erythritol consumption
time frame: 28 weeks (assess 4 weeks after 24 weeks consumption of the study product)
measure: Change in lipid profiles
time frame: 28 weeks (assess 4 weeks after 24 weeks consumption of the study product)
measure: Changes on waist circumference, hip circumference
time frame: 28 weeks (assess 4 weeks after 24 weeks consumption of the study product)
measure: Changes on waist/ hip ratio
time frame: 28 weeks (assess 4 weeks after 24 weeks consumption of the study product)
measure: Adverse events by monitoring clinical and laboratory data
time frame: 28 weeks (assess 4 weeks after 24 weeks consumption of the study product)
arm group label: D-allulose
arm group type: Experimental
description: D-allulose 5 gm 3 times a day
arm group label: erythritol
arm group type: Active Comparator
description: erythritol 5 gm 3 times a day
intervention type: Dietary Supplement
intervention name: D-allulose
description: D-allulose (psicose), a C-3 epimer of D-fructose, is defined one of the rare sugars since it is rarely found in nature. Rare sugars are monosaccharides which present in small quantities in commercial mixtures of D-glucose and D-fructose obtained from hydrolysis of sucrose or isomerization of D-glucose (5). D-allulose (psicose) has been demonstrated to be a non-calorie monosaccharide which has approximately 70% sweetness of sucrose. Various physiological activities of D-allulose (psicose) have been revealed. Of those, its glucose suppressive effect has been proven by both animal and clinical studies.
arm group label: D-allulose
intervention type: Dietary Supplement
intervention name: erythritol
description: non-calorie sweetener
arm group label: erythritol
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Supawan Buranapin, MD
role: Principal Investigator
affiliation: Chiang Mai University
last name: Supawan Buranapin, MD
phone: 66-867310392
email: supawan.b@cmu.ac.th
facility: 
status: Recruiting
contact: 
country: Thailand
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PMID: 4299740
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PMID: 19794929
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PMID: 19155592
citation: Hayashi N, Iida T, Yamada T, Okuma K, Takehara I, Yamamoto T, Yamada K, Tokuda M. Study on the postprandial blood glucose suppression effect of D-psicose in borderline diabetes and the safety of long-term ingestion by normal human subjects. Biosci Biotechnol Biochem. 2010;74(3):510-9. doi: 10.1271/bbb.90707. Epub 2010 Mar 7.
PMID: 20208358
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PMID: 22877751
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PMID: 24144428
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PMID: 21962313
responsible party type: Principal Investigator
investigator affiliation: Chiang Mai University
investigator full name: Supawan Buranapin
investigator title: Assisstant professor
mesh term: Insulin Resistance
mesh term: Erythritol
sharing ipd: No