<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/NCT03793036</url>
  </required_header>
  <id_info>
    <org_study_id>NR01/19</org_study_id>
    <nct_id>NCT03793036</nct_id>
  </id_info>
  <brief_title>Preoperative Administration of Oral Carbohydrate Drink and Postoperative Insulin Resistance</brief_title>
  <official_title>A Randomized Controlled Study of Preoperative Oral Carbohydrate Loading Versus Fasting in Patients Undergoing Colorectal Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nermina Rizvanović</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cantonal Hospital Zenica</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study compared traditional concept of preoperative fasting before elective open colon&#xD;
      surgery and preoperative treatment with carbohydrate oral drink in intention to improve&#xD;
      postoperative stress response to surgical procedure. Hypothesis was: preoperative oral&#xD;
      carbohydrate drink reduces postoperative insulin resistance, improves insulin sensitivity,&#xD;
      reduces postoperative inflammatory response in terms of the value of Glasgow Prognostic Score&#xD;
      (GPS) and IL-6, improves postoperative patient's subjective well-being and surgical clinical&#xD;
      outcome.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This prospective randomized, controlled clinical study was carried out in the Department of&#xD;
      Anesthesiology and Intensive Care Unit and Department of Surgery at the Cantonal Hospital&#xD;
      Zenica, Bosnia and Herzegovina. After obtaining ethical committee approval 50 participants,&#xD;
      scheduled for elective open colon surgery were included into study. Sample size was estimated&#xD;
      using sample size calculator software and power analysis with 95% confidence interval and&#xD;
      power of 80%. Statistical significance was considered as p&lt; 0,05. The calculation indicated&#xD;
      19 participants per group would be sufficient to detect a 50% difference for insulin&#xD;
      resistance between the groups. Assuming dropout would lead to a total sample size of 50&#xD;
      participants. Before each participant agreed to the join the study, the purpose and&#xD;
      procedures of the study were fully explained and informed and written consent was obtained&#xD;
      from each participant. A preoperative anesthetic examination was conducted the day before&#xD;
      surgery. The participants who fulfilled study criteria were randomly allocated into two&#xD;
      groups of 25 participants, depending on the preoperative treatment. The intervention group,&#xD;
      received preoperative carbohydrate oral supplementation (CHO group) and the control group&#xD;
      (FAST group) underwent to a conventional routine of preoperative fasting. Randomization was&#xD;
      performed by computer generated randomization codes. The codes which indicated the treatment&#xD;
      were held in sealed opaque envelopes. Nurse who conducted randomization and opened the&#xD;
      envelopes the night before surgery was blinded to the study protocol as well as the surgeons,&#xD;
      nurses, anesthesiologists and staff involved in data collection.&#xD;
&#xD;
      The participants of FAST group were undergone to the traditional concept of preoperative&#xD;
      fasting before surgical procedure. The participants in the intervention group received&#xD;
      carbohydrate oral supplement at 10:00 pm the evening before surgery and again on the day of&#xD;
      surgery, 2 hours before induction of anesthesia. Assessment of clinical parameters started at&#xD;
      06:00 am on the day of surgery (basal value). The fasting peripheral venous blood samples&#xD;
      were collected to measure serum levels of glucose, insulin, C-reactive protein, albumin and&#xD;
      IL-6, and further 6 hours post-surgery, at 06.00 am on the first postoperative day and at&#xD;
      06:00 am on the second postoperative day. All patients underwent general anesthesia followed&#xD;
      by colon surgery. Assessment of subjective well-being was performed immediately before&#xD;
      induction into anesthesia using a 10 cm horizontal Visual Analogue Scales and then repeated&#xD;
      for 0-4, 4-8, 8-12 and 12-24 hours post-surgery. Pain at rest, pain with mobilization,&#xD;
      thirst, hunger, mouth dryness, anxiety and weakness were evaluated. The patients were&#xD;
      explained how to use the scale. Surgical outcome was evaluated by postoperative return of&#xD;
      gastrointestinal function, time to independent ambulation and postoperative discharge day.&#xD;
      Postoperative data included and the time to oral intake. The following data were recorded&#xD;
      also: age, sex, body weight, body mass index, American Society of Anesthesiologists (ASA)&#xD;
      physical status class, nutritional status of the participants according to Nutritional Risk&#xD;
      Screening 2002 (NRS-2002), tumor localization, type of surgery, duration of surgery,&#xD;
      preoperative fasting time and, blood loss during surgery&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 1, 2018</start_date>
  <completion_date type="Actual">December 31, 2018</completion_date>
  <primary_completion_date type="Actual">December 20, 2018</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>
    <intervention_model_description>The diagnostic protocol for colon cancer was performed in patients at the surgery department. The patients with diagnosed colon tumor were prepared for the surgical procedure. After that, patients were examined to a preoperative anesthetic visit. During the visit, participants were assessed according to eligibility for enrollment in the study. The participants who have met the eligibility criteria have explained the nature of the study protocol. Those who agreed to participate in the study were randomized to one of two study groups for the duration of the study.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Surgeons, anesthetists, and outcome assessors were masking to the treatment allocation. Masking was possible because group allocation was performed by a nurse from the surgical ward, and the attending surgeon and anesthetist welcomed the participants at the operating room the next morning without knowledge of the type of intervention. The outcome study were evaluated by independent assessors who were also masked because they evaluated patients after surgery on a daily base during hospital stay without knowledge of the type intervention.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>The mean change in insulin resistance using computer model Homeostasis model assessment of insulin resistance</measure>
    <time_frame>blood samples were taken at 06:00 am on the day of surgery ( basal value), 6 hours post-surgery, at 06.00 am on the first postoperative day and at 06:00 am on the second postoperative day.</time_frame>
    <description>Blood samples were collected to measure serum levels of glucose and serum levels of insulin. Insulin resistance, was calculated according to the equation = [fasting insulin (µU/ml) x fasting glucose (mmol/L)] / 22,5 using computer model Homeostasis model assessment of insulin resistance 2 Calculator version 2,2. The value &gt;1 indicated the presence of resistance to insulin.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The mean change in Glasgow Prognostic Score (GPS). The GPS was obtained as ratio of serum C-reactive protein/albumin.</measure>
    <time_frame>blood samples were taken at four time points: at 06:00 am on the day of surgery ( basal value), 6 hours post-surgery, at 06.00 am on the first postoperative day and at 06:00 am on the second postoperative day.</time_frame>
    <description>The GPS was calculated as follow: participants with elevated level of C-reactive protein &gt;10mg/L and albumin &lt;35 g/L were allocated a score of 2. Participants showing one or neither of these blood chemistry abnormalities were allocated a score 1 or 0.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The mean change in serum level of IL-6</measure>
    <time_frame>blood samples were taken at four time points: at 06:00 am on the day of surgery ( basal value), 6 hours post-surgery, at 06.00 am on the first postoperative day and at 06:00 am on the second postoperative day.</time_frame>
    <description>The concentration of IL-6 in serum has a r.n. 0-5,9 pg/mL.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The mean change from baseline in participant's subjective well-being score on Visual Analogue Scale</measure>
    <time_frame>The assessment of subjective well-being and pain score was performed immediately before induction into anesthesia and then repeated for 0-4, 4-8, 8-12 and 12-24 hours post-surgery</time_frame>
    <description>The participant's subjective well-being included: pain at rest and with movement, thirst, hunger, dry mouth, weakness, anxiety, nausea and vomiting. The mean change were measured using a 10 cm horizontal Visual Analogue Scale. The scales were undivided and limited at both ends by vertical lines. The left end represented &quot;no symptom&quot; (score:0) and the right end represented &quot;the worst imaginable&quot; (score 100) limits of the variable to be evaluated. The participants rated discomfort by marking on the scales line at the point that represented their level of perceived symptom. The distance on the scales line from score 0 to the patient's mark determined the score of symptom intensity. The score was calculated as follow: 0-1cm no symptom; 1-3 cm mild symptom; 3-7 cm moderate symptom; 7-10 cm strong symptom. The patients were questioned about presence of nausea and vomiting at five study time points. A &quot;NO&quot; answer was grade as 1 and a &quot;YES&quot; answer was graded as 2.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>surgical clinical outcomes</measure>
    <time_frame>from 24 hours post-surgey from apprroximately 10 days post-surgery</time_frame>
    <description>Surgical clinical outcomes included postoperative return of gastrointestinal function, time to independent ambulation and postoperative discharge day. The return of gastrointestinal function was assessed as follow: the sounds of the bowel were detected by an abdominal auscultation 24, 36, 48, 60, 72 and 80 hours after surgery. The time of the first postoperative flatus and defecation were recorded as well as the time to postoperative oral intake.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Insulin Resistance</condition>
  <condition>Inflammatory Response</condition>
  <condition>Exaggerated Well-Being</condition>
  <condition>Length of Stay</condition>
  <arm_group>
    <arm_group_label>FAST group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>preoperative fasting</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CHO group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>preoperative nutrition The participants of experimental group received 400 mil of a clear carbohydrate drink (12,5 gr/100 mil carbohydrate, 50 kcal/100ml, pH 5.0) at 10:00 pm the evening before surgery and another 200 mil of the carbohydrate drink on the day of surgery, 2 hours before induction of anesthesia. After surgery the participants fasted until the recovery of function of the bowel.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>preoperative nutrition</intervention_name>
    <description>The participants of experimental group received 400 mil of a clear carbohydrate drink (12,5 gr/100 mil carbohydrate, 50 kcal/100ml, pH 5.0) at 10:00 pm the evening before surgery and another 200 mil of the carbohydrate drink on the day of surgery, 2 hours before induction of anesthesia. After surgery the participants fasted until the recovery of function of the bowel.</description>
    <arm_group_label>CHO group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  participants with ASA physical status class I-II&#xD;
&#xD;
          -  aged between 18 years and 70 years&#xD;
&#xD;
          -  participants scheduled for elective open colon surgery&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  previous treatment of colon or any other cancer&#xD;
&#xD;
          -  disseminated malignant disease&#xD;
&#xD;
          -  gastro-oesophageal reflux or increased risk of aspiration&#xD;
&#xD;
          -  body mass index below 20 and above 30 kg/m2&#xD;
&#xD;
          -  overall score ≥3 after final assessment of the nutritional status according to&#xD;
             Nutritional Risk Screening 2002 (NRS-2002)&#xD;
&#xD;
          -  emergency colon surgery&#xD;
&#xD;
          -  diabetes mellitus&#xD;
&#xD;
          -  inflammatory bowel disease&#xD;
&#xD;
          -  immunological therapy&#xD;
&#xD;
          -  cardiopulmonary disease&#xD;
&#xD;
          -  neuromusular disease&#xD;
&#xD;
          -  renal disease&#xD;
&#xD;
          -  hepatic or endocrine disease&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
          -  mental disease&#xD;
&#xD;
          -  allergy to any study drugs&#xD;
&#xD;
          -  alcoholic or drug abuse&#xD;
&#xD;
          -  patient's refusal to participate in the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nermina Rizvanović, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cantonal Hospital Zenica, Crkvice 67, 72 000 Zenica, Bosnia and Herzegovina</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cantonal Hospital Zenica</name>
      <address>
        <city>Zenica</city>
        <zip>72 000</zip>
        <country>Bosnia and Herzegovina</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Bosnia and Herzegovina</country>
  </location_countries>
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  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 2, 2019</study_first_submitted>
  <study_first_submitted_qc>January 2, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 4, 2019</study_first_posted>
  <last_update_submitted>January 3, 2019</last_update_submitted>
  <last_update_submitted_qc>January 3, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 7, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Cantonal Hospital Zenica</investigator_affiliation>
    <investigator_full_name>Nermina Rizvanović</investigator_full_name>
    <investigator_title>MD Anesthesiology and Intensive Care Specialist</investigator_title>
  </responsible_party>
  <keyword>fasting</keyword>
  <keyword>carbohydrate</keyword>
  <keyword>insulin resistance</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Insulin Resistance</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03793036
org study id: NR01/19
nct id: NCT03793036
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study compared traditional concept of preoperative fasting before elective open colon
      surgery and preoperative treatment with carbohydrate oral drink in intention to improve
      postoperative stress response to surgical procedure. Hypothesis was: preoperative oral
      carbohydrate drink reduces postoperative insulin resistance, improves insulin sensitivity,
      reduces postoperative inflammatory response in terms of the value of Glasgow Prognostic Score
      (GPS) and IL-6, improves postoperative patient's subjective well-being and surgical clinical
      outcome.
This prospective randomized, controlled clinical study was carried out in the Department of
      Anesthesiology and Intensive Care Unit and Department of Surgery at the Cantonal Hospital
      Zenica, Bosnia and Herzegovina. After obtaining ethical committee approval 50 participants,
      scheduled for elective open colon surgery were included into study. Sample size was estimated
      using sample size calculator software and power analysis with 95% confidence interval and
      power of 80%. Statistical significance was considered as p< 0,05. The calculation indicated
      19 participants per group would be sufficient to detect a 50% difference for insulin
      resistance between the groups. Assuming dropout would lead to a total sample size of 50
      participants. Before each participant agreed to the join the study, the purpose and
      procedures of the study were fully explained and informed and written consent was obtained
      from each participant. A preoperative anesthetic examination was conducted the day before
      surgery. The participants who fulfilled study criteria were randomly allocated into two
      groups of 25 participants, depending on the preoperative treatment. The intervention group,
      received preoperative carbohydrate oral supplementation (CHO group) and the control group
      (FAST group) underwent to a conventional routine of preoperative fasting. Randomization was
      performed by computer generated randomization codes. The codes which indicated the treatment
      were held in sealed opaque envelopes. Nurse who conducted randomization and opened the
      envelopes the night before surgery was blinded to the study protocol as well as the surgeons,
      nurses, anesthesiologists and staff involved in data collection.

      The participants of FAST group were undergone to the traditional concept of preoperative
      fasting before surgical procedure. The participants in the intervention group received
      carbohydrate oral supplement at 10:00 pm the evening before surgery and again on the day of
      surgery, 2 hours before induction of anesthesia. Assessment of clinical parameters started at
      06:00 am on the day of surgery (basal value). The fasting peripheral venous blood samples
      were collected to measure serum levels of glucose, insulin, C-reactive protein, albumin and
      IL-6, and further 6 hours post-surgery, at 06.00 am on the first postoperative day and at
      06:00 am on the second postoperative day. All patients underwent general anesthesia followed
      by colon surgery. Assessment of subjective well-being was performed immediately before
      induction into anesthesia using a 10 cm horizontal Visual Analogue Scales and then repeated
      for 0-4, 4-8, 8-12 and 12-24 hours post-surgery. Pain at rest, pain with mobilization,
      thirst, hunger, mouth dryness, anxiety and weakness were evaluated. The patients were
      explained how to use the scale. Surgical outcome was evaluated by postoperative return of
      gastrointestinal function, time to independent ambulation and postoperative discharge day.
      Postoperative data included and the time to oral intake. The following data were recorded
      also: age, sex, body weight, body mass index, American Society of Anesthesiologists (ASA)
      physical status class, nutritional status of the participants according to Nutritional Risk
      Screening 2002 (NRS-2002), tumor localization, type of surgery, duration of surgery,
      preoperative fasting time and, blood loss during surgery
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: The diagnostic protocol for colon cancer was performed in patients at the surgery department. The patients with diagnosed colon tumor were prepared for the surgical procedure. After that, patients were examined to a preoperative anesthetic visit. During the visit, participants were assessed according to eligibility for enrollment in the study. The participants who have met the eligibility criteria have explained the nature of the study protocol. Those who agreed to participate in the study were randomized to one of two study groups for the duration of the study.
primary purpose: Treatment
masking: Triple (Care Provider, Investigator, Outcomes Assessor)
masking description: Surgeons, anesthetists, and outcome assessors were masking to the treatment allocation. Masking was possible because group allocation was performed by a nurse from the surgical ward, and the attending surgeon and anesthetist welcomed the participants at the operating room the next morning without knowledge of the type of intervention. The outcome study were evaluated by independent assessors who were also masked because they evaluated patients after surgery on a daily base during hospital stay without knowledge of the type intervention.
measure: The mean change in insulin resistance using computer model Homeostasis model assessment of insulin resistance
time frame: blood samples were taken at 06:00 am on the day of surgery ( basal value), 6 hours post-surgery, at 06.00 am on the first postoperative day and at 06:00 am on the second postoperative day.
description: Blood samples were collected to measure serum levels of glucose and serum levels of insulin. Insulin resistance, was calculated according to the equation = [fasting insulin (µU/ml) x fasting glucose (mmol/L)] / 22,5 using computer model Homeostasis model assessment of insulin resistance 2 Calculator version 2,2. The value >1 indicated the presence of resistance to insulin.
measure: The mean change in Glasgow Prognostic Score (GPS). The GPS was obtained as ratio of serum C-reactive protein/albumin.
time frame: blood samples were taken at four time points: at 06:00 am on the day of surgery ( basal value), 6 hours post-surgery, at 06.00 am on the first postoperative day and at 06:00 am on the second postoperative day.
description: The GPS was calculated as follow: participants with elevated level of C-reactive protein >10mg/L and albumin <35 g/L were allocated a score of 2. Participants showing one or neither of these blood chemistry abnormalities were allocated a score 1 or 0.
measure: The mean change in serum level of IL-6
time frame: blood samples were taken at four time points: at 06:00 am on the day of surgery ( basal value), 6 hours post-surgery, at 06.00 am on the first postoperative day and at 06:00 am on the second postoperative day.
description: The concentration of IL-6 in serum has a r.n. 0-5,9 pg/mL.
measure: The mean change from baseline in participant's subjective well-being score on Visual Analogue Scale
time frame: The assessment of subjective well-being and pain score was performed immediately before induction into anesthesia and then repeated for 0-4, 4-8, 8-12 and 12-24 hours post-surgery
description: The participant's subjective well-being included: pain at rest and with movement, thirst, hunger, dry mouth, weakness, anxiety, nausea and vomiting. The mean change were measured using a 10 cm horizontal Visual Analogue Scale. The scales were undivided and limited at both ends by vertical lines. The left end represented "no symptom" (score:0) and the right end represented "the worst imaginable" (score 100) limits of the variable to be evaluated. The participants rated discomfort by marking on the scales line at the point that represented their level of perceived symptom. The distance on the scales line from score 0 to the patient's mark determined the score of symptom intensity. The score was calculated as follow: 0-1cm no symptom; 1-3 cm mild symptom; 3-7 cm moderate symptom; 7-10 cm strong symptom. The patients were questioned about presence of nausea and vomiting at five study time points. A "NO" answer was grade as 1 and a "YES" answer was graded as 2.
measure: surgical clinical outcomes
time frame: from 24 hours post-surgey from apprroximately 10 days post-surgery
description: Surgical clinical outcomes included postoperative return of gastrointestinal function, time to independent ambulation and postoperative discharge day. The return of gastrointestinal function was assessed as follow: the sounds of the bowel were detected by an abdominal auscultation 24, 36, 48, 60, 72 and 80 hours after surgery. The time of the first postoperative flatus and defecation were recorded as well as the time to postoperative oral intake.
arm group label: FAST group
arm group type: No Intervention
description: preoperative fasting
arm group label: CHO group
arm group type: Experimental
description: preoperative nutrition The participants of experimental group received 400 mil of a clear carbohydrate drink (12,5 gr/100 mil carbohydrate, 50 kcal/100ml, pH 5.0) at 10:00 pm the evening before surgery and another 200 mil of the carbohydrate drink on the day of surgery, 2 hours before induction of anesthesia. After surgery the participants fasted until the recovery of function of the bowel.
intervention type: Dietary Supplement
intervention name: preoperative nutrition
description: The participants of experimental group received 400 mil of a clear carbohydrate drink (12,5 gr/100 mil carbohydrate, 50 kcal/100ml, pH 5.0) at 10:00 pm the evening before surgery and another 200 mil of the carbohydrate drink on the day of surgery, 2 hours before induction of anesthesia. After surgery the participants fasted until the recovery of function of the bowel.
arm group label: CHO group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Nermina Rizvanović, MD
role: Principal Investigator
affiliation: Cantonal Hospital Zenica, Crkvice 67, 72 000 Zenica, Bosnia and Herzegovina
facility: 
country: Bosnia and Herzegovina
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responsible party type: Sponsor-Investigator
investigator affiliation: Cantonal Hospital Zenica
investigator full name: Nermina Rizvanović
investigator title: MD Anesthesiology and Intensive Care Specialist
mesh term: Insulin Resistance
sharing ipd: Undecided