<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/NCT03805139</url>
  </required_header>
  <id_info>
    <org_study_id>122</org_study_id>
    <nct_id>NCT03805139</nct_id>
  </id_info>
  <brief_title>Role of Ajwa Derived Polyphenols in Dyslipidaemias</brief_title>
  <official_title>Role of Ajwa Derived Polyphenols in Dyslipidaemias</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Aga Khan University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Aga Khan University</source>
  <oversight_info>
    <has_dmc>No</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>
      World Health Organization report notifies of the escalating global burden of cardiovascular&#xD;
      diseases (CVD), projecting that it will become the major worldwide cause of death and&#xD;
      disability by 2020. The South Asian countries have the highest rates of CVD globally. It is&#xD;
      widely acknowledged that South Asians have 40-60% higher risk of CVD linked to mortality,&#xD;
      compared with other populations. Multiple human population studies have established the&#xD;
      concentration of high density lipoprotein (HDL) cholesterol as an independent, inverse&#xD;
      predictor of the risk of having a cardiovascular event. Furthermore, HDLs have several&#xD;
      well-documented functions with the potential to protect against cardiovascular disease. This&#xD;
      study trial is designed to find out the role of alternative medicine such as functional food&#xD;
      to improve the dyslipidemia and particularly increase the levels of HDL in general&#xD;
      population. We expect that the use of Ajwa dates will significantly enhance the level of HDL&#xD;
      and reduce cardiovascular events in general population.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Overall lipid profile is important in cardiovascular diseases but particularly serum HDL&#xD;
      levels have long been recognized as an independent inverse prognostic marker of CVD, when the&#xD;
      Framigham study, in 1980s showed that HDL below 40-60mg/dl is of prognostic relevance. A rise&#xD;
      of 1mg/dl in HDL levels is considered to reduce coronary artery disease (CAD) risk to 2-3%.&#xD;
      Even patients with elevated total cholesterol (TC) and LDL, presenting a high HDL are seen to&#xD;
      be protected from atherosclerosis. Multiple human population studies have shown the&#xD;
      concentration of HDL cholesterol as an independent, inverse predictor of the risk of having a&#xD;
      cardiovascular event. Additionally, HDL has several well-documented functions with the&#xD;
      potential to protect against cardiovascular diseases. These include an ability to promote the&#xD;
      efflux of cholesterol from macrophages in the artery wall, inhibit the oxidative modification&#xD;
      of LDL, inhibit vascular inflammation, inhibit thrombosis, promote endothelial repair,&#xD;
      promote angiogenesis, anti-oxidant, enhance endothelial function, improve diabetic control,&#xD;
      and inhibit hematopoietic stem cell proliferation. HDL also exerts direct cardio protective&#xD;
      effect, which are mediated with its interactions with the myocardium.&#xD;
&#xD;
      Various studies have emphasised the high incidence of CVD within the South Asian countries.&#xD;
      The increased risk of cardiovascular events in South Asians at a younger age might be due to&#xD;
      unknown factors affecting plaque rupture, the interaction between prothrombotic factors and&#xD;
      atherosclerosis, or may be due to any undiscovered risk factors. Urbanisation and&#xD;
      westernisation is characterised by a distinct increase in the intake of energy dense foods, a&#xD;
      decrease in physical activity, and a heightened level of psychosocial stress, all of which&#xD;
      promote the development of hyperglycaemia, hypertension, and dyslipidaemia. Most common&#xD;
      dyslipidaemia in South Asians is low HDL-C and high triglycerides. High triglyceride and low&#xD;
      HDL-C levels are metabolically interlinked. This metabolic phenotype is also associated with&#xD;
      increased levels of small LDL particles despite relatively normal levels of LDL-C among South&#xD;
      Asians. This clinical syndrome is accompanied by insulin resistance, a condition frequently&#xD;
      referred to as atherogenic dyslipidemia, which is a common metabolic derangement among Asian.&#xD;
      South Asians not only have lower HDL levels but also have a higher concentration of small,&#xD;
      less-protective HDL particles. One proposed mechanism is presence of dysfunctional HDL&#xD;
      particles. Another potential explanation for the apparent blunted cardioprotection of HDL in&#xD;
      South Asians might be related to HDL particle size. Small particles might be less efficient&#xD;
      in reverse cholesterol transport. In general, HDL particle size tends to be lower in patients&#xD;
      with CHD and those with low HDL-C levels . Alarmingly, an estimated 60-80% of Pakistani&#xD;
      population has been reported to have low HDL. There are a number of non-pharmacological and&#xD;
      pharmacological recommendations for management of low HDL. Non-pharmacological (functional&#xD;
      food) strategies are reported to increase HDL levels around 10-15% and which include regular&#xD;
      exercise , body weight reduction in obese individuals , cessation of cigarette smoking in&#xD;
      smokers and dietary modifications like decrease intake of saturated trans-fatty acids with&#xD;
      increase intake of omega-3 polyunsaturated fatty acids . There are also a number of&#xD;
      pharmacological agents being considered as therapeutic options but the tolerability and&#xD;
      safety issues limit their use in addition to limited success in improving HDL. Therefore, the&#xD;
      focus of research now days had been toward the use of functional food which can play&#xD;
      significant role in cardiac protection. Ajwa dates have been recognized to contain the&#xD;
      nutritional and medicinal properties. These are a rich source of nutrition, containing&#xD;
      sugars, proteins, vitamins, high dietary fibres, minerals and fats, various phytochemicals&#xD;
      like sterols, polyphenols, flavonoids and glycosides. Ajwa fruit is gifted by nature and is&#xD;
      enriched with polyphenols and can act as a protective agent against many diseases. Various&#xD;
      studies have been conducted to investigate the presence of different polyphenols in Ajwa.&#xD;
      Different researchers have determined different phenolic components&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">March 20, 2019</start_date>
  <completion_date type="Anticipated">December 7, 2019</completion_date>
  <primary_completion_date type="Actual">November 7, 2019</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>A total of 60 subjects (30 in each group) will be included in the study. The total duration of study will be upto 6 months. The AKU faculty and staff will be invited to MDL lab for screening and initial baseline, enrolled participant will be informed for inclusion in the research on the basis of our criteria of HDL levels. Written informed consent (a copy will also be provided to the participant) will be taken from each individual. A questionnaire regarding their diet and life style will be filled. Following vitals will be measured body weight, height and blood pressure. Blood sample will be taken for lipid profile (LDL, HDL, total cholesterol and triglycerides). Total period for each participant will be 6 weeks for interventions. In Ajwa Dates group, number of interaction will be 5 days a week for 6 weeks (30 doses will be provided).</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Lipid profile</measure>
    <time_frame>6 weeks</time_frame>
    <description>Increase in HDL 3mg/dl, decrease LDL, TG, TC reduction in LDL, Triglycerides, total cholesterol 5mg/dl</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Lipid profile</measure>
    <time_frame>6 weeks</time_frame>
    <description>reduction in LDL</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Lipid profile</measure>
    <time_frame>6 weeks</time_frame>
    <description>reduction in triglycerides</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Lipid profile</measure>
    <time_frame>6 weeks</time_frame>
    <description>reduction in Total cholesterol</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Lipid profile</measure>
    <time_frame>6 weeks</time_frame>
    <description>Increase in HDL 3mg/dl reduction in LDL, Triglycerides, total cholesterol 5mg/dl</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Lipid profile</measure>
    <time_frame>6 weeks</time_frame>
    <description>reduced insulin resistance reduction in LDL, Triglycerides, total cholesterol 5mg/dl</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Dyslipidemias</condition>
  <condition>Hyperglycemia</condition>
  <condition>Liver Dysfunction</condition>
  <condition>Oxidative Stress</condition>
  <condition>Hemoglobin SC</condition>
  <condition>Anemia</condition>
  <arm_group>
    <arm_group_label>Ajwa Dates group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>55-65gms Ajwa dates 7 days a week for 6 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>No intervention</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Ajwa Date (phoenix dactylifera)</intervention_name>
    <description>Effect of Ajwa on Dyslipidemia</description>
    <arm_group_label>Ajwa Dates group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        INCLUSION CRITERIA:&#xD;
&#xD;
          -  General population from AKU with serum HDL &lt; 40 mg/dl for men and women&#xD;
&#xD;
          -  Adult ages (18- 70years ) will be included in the study.&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
          -  Individuals with Dates/Ajwa allergy&#xD;
&#xD;
          -  Individuals Patients already taking regular Ajwa&#xD;
&#xD;
          -  Pregnant women and individuals with diabetes, metabolic syndrome or any other&#xD;
             co-morbidity will be excluded.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Aga Khan University</name>
      <address>
        <city>Karachi</city>
        <state>Sindh</state>
        <zip>74800</zip>
        <country>Pakistan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>NASEER AHMED</last_name>
      <phone>3333382013</phone>
      <email>dr.naseer99@gmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>Pakistan</country>
  </location_countries>
  <reference>
    <citation>1.Rocha-Guzmán NE, Herzog A, González-Laredo RF, Ibarra-Pérez FJ, Zambrano-Galván G, Gallegos-Infante JA: Antioxidant and antimutagenic activity of phenolic compounds in three different colour groups of common bean cultivars (Phaseolus vulgaris). Food Chemistry 2007, 103:521-527. 2. Majewska-Wierzbicka M, Czeczot H: [Flavonoids in the prevention and treatment of cardiovascular diseases]. Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego 2012, 32:50-54. 3. Salvamani S, Gunasekaran B, Shaharuddin NA, Ahmad SA, Shukor MY: Antiartherosclerotic effects of plant flavonoids. BioMed research international 2014, 2014:480258. 4. Norata GD, Marchesi P, Passamonti S, Pirillo A, Violi F, Catapano AL: Anti-inflammatory and anti-atherogenic effects of cathechin, caffeic acid and trans-resveratrol in apolipoprotein E deficient mice. Atherosclerosis 2007, 191:265-271. 5. Riccioni G, Gammone MA, Tettamanti G, Bergante S, Pluchinotta FR, D'Orazio N: Resveratrol and anti-atherogenic effects. International journal of food sciences and nutrition 2015, 66:603-610.</citation>
  </reference>
  <verification_date>November 2019</verification_date>
  <study_first_submitted>January 11, 2019</study_first_submitted>
  <study_first_submitted_qc>January 14, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 15, 2019</study_first_posted>
  <last_update_submitted>November 7, 2019</last_update_submitted>
  <last_update_submitted_qc>November 7, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 12, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Aga Khan University</investigator_affiliation>
    <investigator_full_name>NASEER AHMED</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>Ajwa (Pheonix Dactylfera) Derived polyphenol</keyword>
  <keyword>Dyslipidemia</keyword>
  <keyword>Cardioprotection</keyword>
  <keyword>HDL</keyword>
  <keyword>Transferulic Acid</keyword>
  <keyword>Gallic Acid</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Diseases</mesh_term>
    <mesh_term>Hemoglobin SC Disease</mesh_term>
    <mesh_term>Dyslipidemias</mesh_term>
    <mesh_term>Hyperglycemia</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/NCT03805139
org study id: 122
nct id: NCT03805139
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
World Health Organization report notifies of the escalating global burden of cardiovascular
      diseases (CVD), projecting that it will become the major worldwide cause of death and
      disability by 2020. The South Asian countries have the highest rates of CVD globally. It is
      widely acknowledged that South Asians have 40-60% higher risk of CVD linked to mortality,
      compared with other populations. Multiple human population studies have established the
      concentration of high density lipoprotein (HDL) cholesterol as an independent, inverse
      predictor of the risk of having a cardiovascular event. Furthermore, HDLs have several
      well-documented functions with the potential to protect against cardiovascular disease. This
      study trial is designed to find out the role of alternative medicine such as functional food
      to improve the dyslipidemia and particularly increase the levels of HDL in general
      population. We expect that the use of Ajwa dates will significantly enhance the level of HDL
      and reduce cardiovascular events in general population.
Overall lipid profile is important in cardiovascular diseases but particularly serum HDL
      levels have long been recognized as an independent inverse prognostic marker of CVD, when the
      Framigham study, in 1980s showed that HDL below 40-60mg/dl is of prognostic relevance. A rise
      of 1mg/dl in HDL levels is considered to reduce coronary artery disease (CAD) risk to 2-3%.
      Even patients with elevated total cholesterol (TC) and LDL, presenting a high HDL are seen to
      be protected from atherosclerosis. Multiple human population studies have shown the
      concentration of HDL cholesterol as an independent, inverse predictor of the risk of having a
      cardiovascular event. Additionally, HDL has several well-documented functions with the
      potential to protect against cardiovascular diseases. These include an ability to promote the
      efflux of cholesterol from macrophages in the artery wall, inhibit the oxidative modification
      of LDL, inhibit vascular inflammation, inhibit thrombosis, promote endothelial repair,
      promote angiogenesis, anti-oxidant, enhance endothelial function, improve diabetic control,
      and inhibit hematopoietic stem cell proliferation. HDL also exerts direct cardio protective
      effect, which are mediated with its interactions with the myocardium.

      Various studies have emphasised the high incidence of CVD within the South Asian countries.
      The increased risk of cardiovascular events in South Asians at a younger age might be due to
      unknown factors affecting plaque rupture, the interaction between prothrombotic factors and
      atherosclerosis, or may be due to any undiscovered risk factors. Urbanisation and
      westernisation is characterised by a distinct increase in the intake of energy dense foods, a
      decrease in physical activity, and a heightened level of psychosocial stress, all of which
      promote the development of hyperglycaemia, hypertension, and dyslipidaemia. Most common
      dyslipidaemia in South Asians is low HDL-C and high triglycerides. High triglyceride and low
      HDL-C levels are metabolically interlinked. This metabolic phenotype is also associated with
      increased levels of small LDL particles despite relatively normal levels of LDL-C among South
      Asians. This clinical syndrome is accompanied by insulin resistance, a condition frequently
      referred to as atherogenic dyslipidemia, which is a common metabolic derangement among Asian.
      South Asians not only have lower HDL levels but also have a higher concentration of small,
      less-protective HDL particles. One proposed mechanism is presence of dysfunctional HDL
      particles. Another potential explanation for the apparent blunted cardioprotection of HDL in
      South Asians might be related to HDL particle size. Small particles might be less efficient
      in reverse cholesterol transport. In general, HDL particle size tends to be lower in patients
      with CHD and those with low HDL-C levels . Alarmingly, an estimated 60-80% of Pakistani
      population has been reported to have low HDL. There are a number of non-pharmacological and
      pharmacological recommendations for management of low HDL. Non-pharmacological (functional
      food) strategies are reported to increase HDL levels around 10-15% and which include regular
      exercise , body weight reduction in obese individuals , cessation of cigarette smoking in
      smokers and dietary modifications like decrease intake of saturated trans-fatty acids with
      increase intake of omega-3 polyunsaturated fatty acids . There are also a number of
      pharmacological agents being considered as therapeutic options but the tolerability and
      safety issues limit their use in addition to limited success in improving HDL. Therefore, the
      focus of research now days had been toward the use of functional food which can play
      significant role in cardiac protection. Ajwa dates have been recognized to contain the
      nutritional and medicinal properties. These are a rich source of nutrition, containing
      sugars, proteins, vitamins, high dietary fibres, minerals and fats, various phytochemicals
      like sterols, polyphenols, flavonoids and glycosides. Ajwa fruit is gifted by nature and is
      enriched with polyphenols and can act as a protective agent against many diseases. Various
      studies have been conducted to investigate the presence of different polyphenols in Ajwa.
      Different researchers have determined different phenolic components
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: A total of 60 subjects (30 in each group) will be included in the study. The total duration of study will be upto 6 months. The AKU faculty and staff will be invited to MDL lab for screening and initial baseline, enrolled participant will be informed for inclusion in the research on the basis of our criteria of HDL levels. Written informed consent (a copy will also be provided to the participant) will be taken from each individual. A questionnaire regarding their diet and life style will be filled. Following vitals will be measured body weight, height and blood pressure. Blood sample will be taken for lipid profile (LDL, HDL, total cholesterol and triglycerides). Total period for each participant will be 6 weeks for interventions. In Ajwa Dates group, number of interaction will be 5 days a week for 6 weeks (30 doses will be provided).
primary purpose: Treatment
masking: None (Open Label)
measure: Lipid profile
time frame: 6 weeks
description: Increase in HDL 3mg/dl, decrease LDL, TG, TC reduction in LDL, Triglycerides, total cholesterol 5mg/dl
measure: Lipid profile
time frame: 6 weeks
description: reduction in LDL
measure: Lipid profile
time frame: 6 weeks
description: reduction in triglycerides
measure: Lipid profile
time frame: 6 weeks
description: reduction in Total cholesterol
measure: Lipid profile
time frame: 6 weeks
description: Increase in HDL 3mg/dl reduction in LDL, Triglycerides, total cholesterol 5mg/dl
measure: Lipid profile
time frame: 6 weeks
description: reduced insulin resistance reduction in LDL, Triglycerides, total cholesterol 5mg/dl
arm group label: Ajwa Dates group
arm group type: Experimental
description: 55-65gms Ajwa dates 7 days a week for 6 weeks
arm group label: Control
arm group type: No Intervention
description: No intervention
intervention type: Dietary Supplement
intervention name: Ajwa Date (phoenix dactylifera)
description: Effect of Ajwa on Dyslipidemia
arm group label: Ajwa Dates group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
status: Recruiting
contact: 
country: Pakistan
citation: 1.Rocha-Guzmán NE, Herzog A, González-Laredo RF, Ibarra-Pérez FJ, Zambrano-Galván G, Gallegos-Infante JA: Antioxidant and antimutagenic activity of phenolic compounds in three different colour groups of common bean cultivars (Phaseolus vulgaris). Food Chemistry 2007, 103:521-527. 2. Majewska-Wierzbicka M, Czeczot H: [Flavonoids in the prevention and treatment of cardiovascular diseases]. Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego 2012, 32:50-54. 3. Salvamani S, Gunasekaran B, Shaharuddin NA, Ahmad SA, Shukor MY: Antiartherosclerotic effects of plant flavonoids. BioMed research international 2014, 2014:480258. 4. Norata GD, Marchesi P, Passamonti S, Pirillo A, Violi F, Catapano AL: Anti-inflammatory and anti-atherogenic effects of cathechin, caffeic acid and trans-resveratrol in apolipoprotein E deficient mice. Atherosclerosis 2007, 191:265-271. 5. Riccioni G, Gammone MA, Tettamanti G, Bergante S, Pluchinotta FR, D'Orazio N: Resveratrol and anti-atherogenic effects. International journal of food sciences and nutrition 2015, 66:603-610.
responsible party type: Principal Investigator
investigator affiliation: Aga Khan University
investigator full name: NASEER AHMED
investigator title: Assistant Professor
mesh term: Liver Diseases
mesh term: Hemoglobin SC Disease
mesh term: Dyslipidemias
mesh term: Hyperglycemia
sharing ipd: Undecided