<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/NCT03260803</url>
  </required_header>
  <id_info>
    <org_study_id>34606</org_study_id>
    <nct_id>NCT03260803</nct_id>
  </id_info>
  <brief_title>Oligopin Supplementation and Bone Turnover Markers and Antioxidant Changes in Postmenopausal Osteopenic Women</brief_title>
  <official_title>Valuating the Effects of Oligopin Supplementation on the Turnover of Bone Formation and Antioxidant Changes in Postmenopausal Osteopenic Women: A Randomized Double-blind Clinical Trial With Placebo-concurrent Controls</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tehran University of Medical Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Iran University of Medical Sciences</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Tehran University of Medical Sciences</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>
      Osteoporosis fractures impose a significant economic burden on the health system. There is&#xD;
      evidence that osteoporosis has a high prevalence in Iran (4.8% for men and 7.7% for women),&#xD;
      and the frequency of osteopenia is 36.8% for men and 39.3% for women in Iran Accordingly, the&#xD;
      prevention of osteopenia progression towards osteoporosis has been considered as an important&#xD;
      issue in medicine. Bone is a dynamic tissue that is constantly being remodeled thus the&#xD;
      equilibrium between bone formation and resorption done by simultaneously regulating&#xD;
      osteoclasts and osteoblasts is important. Imbalance between bone deposition and resorption&#xD;
      contributes to reducing bone mineral density and hence increasing the risk of osteoporosis&#xD;
&#xD;
      Recently, new therapies have been focused on use of medicinal herbs, especially&#xD;
      phytochemicals. Among phytochemicals, phytonutrients, and especially polyphenols, can act&#xD;
      both on osteoblast and on osteoclast.&#xD;
&#xD;
      Pine bark extract (oligopin) is a rich source of polyphenols that exerts strong antioxidant&#xD;
      and anti-inflammatory activities. It has also beneficial effects on bone turnover based on in&#xD;
      vitro studies and animal models. Investigators aimed to investigate the effects of oligopin&#xD;
      on bone turnover markers and plasma and peripheral mononuclear cells oxidative stress in&#xD;
      postmenopausal women with osteopenia in a double-blind randomized clinical trial.&#xD;
      Participants are forty four women with osteopenia divided into two groups randomly (22,&#xD;
      having oligopin, 150 mg, once daily, for 12 weeks). The 2nd group (22 women with osteopenia)&#xD;
      receives the same amount of the placebo. At the first and the end of the study, blood sample&#xD;
      are taken to measure in order to peripheral blood mononuclear cells isolation and plasma&#xD;
      separation. The levels of bone alkaline phosphatase and carboxy terminal collagen type I in&#xD;
      plasma oxidative stress markers such as total anti-oxidant capacity, malondialdehyde, and&#xD;
      protein carbonyl were evaluated. Furthermore, oxidative stress will be evaluated in&#xD;
      peripheral blood mononuclear cells by measurement of expression and activity of magnesium&#xD;
      superoxide dismutase,catalase and Nuclear factor (erythroid-derived 2)-like 2.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 1, 2018</start_date>
  <completion_date type="Actual">March 1, 2019</completion_date>
  <primary_completion_date type="Actual">December 1, 2018</primary_completion_date>
  <phase>Phase 3</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>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Plasma Osteocalcin Concentration</measure>
    <time_frame>up to third month after intervention</time_frame>
    <description>Osteocalcin levels in plasma</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma Carboxyl terminal collagen type I Concentration</measure>
    <time_frame>up to third month after intervention</time_frame>
    <description>Carboxyl terminal collagen type I in plasma</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Osteocalcin/Carboxyl terminal collagen type I ratio</measure>
    <time_frame>up to third month after intervention</time_frame>
    <description>Osteocalcin/Carboxyl terminal collagen type I ratio</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>MnSOD activity in peripheral blood mononuclear cells</measure>
    <time_frame>Baseline and third month after intervention</time_frame>
    <description>MnSOD activity in peripheral blood mononuclear cells</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Catalase activity in peripheral blood mononuclear cells</measure>
    <time_frame>Baseline and third month after intervention</time_frame>
    <description>Catalase activity in peripheral blood mono nuclear cells</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MnSOD mRNA expression peripheral blood mononuclear cells</measure>
    <time_frame>Baseline and third month after intervention</time_frame>
    <description>MnSOD mRNA expression peripheral blood mononuclear cells</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Catalase mRNA expression peripheral blood mononuclear cells</measure>
    <time_frame>Baseline and third month after intervention</time_frame>
    <description>Catalase mRNA expression peripheral blood mononuclear cells</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NrF2 mRNA expression peripheral blood mononuclear cells</measure>
    <time_frame>Baseline and third month after intervention</time_frame>
    <description>NrF2 mRNA expression peripheral blood mononuclear cells</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Malondialdehide Concentration</measure>
    <time_frame>Baseline and third month after intervention</time_frame>
    <description>Malondialdehide levels in plasma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>total antioxidant capacity</measure>
    <time_frame>Baseline and third month after intervention</time_frame>
    <description>total antioxidant capacity in plasma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>protein carbonyl content</measure>
    <time_frame>Baseline and third month after intervention</time_frame>
    <description>protein carbonyl content in plasma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Total thiol concentration</measure>
    <time_frame>Baseline and third month after intervention</time_frame>
    <description>Total thiol level in plasma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Catalase activity in Plasma</measure>
    <time_frame>Baseline and third month after intervention</time_frame>
    <description>Catalase activity in plasma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MnSOD activity in Plasma</measure>
    <time_frame>Baseline and third month after intervention</time_frame>
    <description>MnSOD activity in plasma</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">43</enrollment>
  <condition>Osteopenia</condition>
  <arm_group>
    <arm_group_label>postmenopausal osteopenic women receiveing Oligopin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>postmenopausal osteopenic women receiving Oligopin ,150 mg ,once daily, 12 week</description>
  </arm_group>
  <arm_group>
    <arm_group_label>postmenopausal osteopenic women receiving placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>postmenopausal osteopenic women receiving placebo, 150 mg,once daily,12 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Oligopin</intervention_name>
    <description>Oligopin ,150 mg ,once daily, 12 week</description>
    <arm_group_label>postmenopausal osteopenic women receiveing Oligopin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo,150 mg ,once daily, 12 week</description>
    <arm_group_label>postmenopausal osteopenic women receiving placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Inclusion criteria: Postmenopausal women; Aged between 50-65; Diagnosis of osteopenia&#xD;
             based on Tscore ( -2.5 SD ≤ Tscore ≤ -1 SD); To have equal physical, pediatric and&#xD;
             complementary therapies for at least three months before entrance to study ;Absence of&#xD;
             history of Bone Diseases; Absence of the history of chronic diseases including cancer,&#xD;
             diabetes, kidney failure, liver disease, systemic inflammatory diseases, degenerative&#xD;
             joint diseases and rheumatologic disorders, primary thalassemia, hyperparathyroidism,&#xD;
             hyperthyroidism-Cushing's, Hypercalcaemia syndrome, Hyperglycemia ;Absence of&#xD;
             gastrointestinal disease including Crohn's disease, ulcerative colitis, celiac&#xD;
             disease, and chronic diarrhea and gastric or duodenal ulcers treated or with a history&#xD;
             of gastrointestinal bleeding (according to the patient's history); Absence of history&#xD;
             of the use of drugs that affect bone metabolism and have been regularly used for at&#xD;
             least 6 months in the past two years: such as osteoporosis drugs (bisphosphonates,&#xD;
             estrogen receptor selective agonists / selective antagonists, alternative HRTs, PTH),&#xD;
             diuretics, thiazides, anticonvulsants (phenytoin, phenobarbital, sodium valproate),&#xD;
             glucocorticoids, nonsteroidal anti-inflammatory drugs such as analgesics (nonsteroidal&#xD;
             anti-inflammatory drugs such as naproxen, aspirin and ibuprofen), cigarettes; Absence&#xD;
             of motor disabilities, skeletal disorders, untreated psychiatric illnesses such as&#xD;
             psychosis, Alzheimer's disease, Parkinson's disease; To accept randomization; Absence&#xD;
             of morbid Obesity: BMI is above 40&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Fracture report during the study period; Unwillingness of participants to continue the&#xD;
        project; The occurrence of any visible side effects of supplemental effects&#xD;
&#xD;
        -&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Tehran University of Medical Sciences</name>
      <address>
        <city>Tehran</city>
        <zip>0098</zip>
        <country>Iran, Islamic Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Iran, Islamic Republic of</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>August 22, 2017</study_first_submitted>
  <study_first_submitted_qc>August 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 24, 2017</study_first_posted>
  <last_update_submitted>May 18, 2020</last_update_submitted>
  <last_update_submitted_qc>May 18, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 20, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Tehran University of Medical Sciences</investigator_affiliation>
    <investigator_full_name>Solaleh EmamGholi</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>osteopenia</keyword>
  <keyword>oligopin</keyword>
  <keyword>postmenopause</keyword>
  <keyword>antioxidant</keyword>
  <keyword>bone</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bone Diseases, Metabolic</mesh_term>
  </condition_browse>
  <!-- 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/NCT03260803
org study id: 34606
nct id: NCT03260803
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Osteoporosis fractures impose a significant economic burden on the health system. There is
      evidence that osteoporosis has a high prevalence in Iran (4.8% for men and 7.7% for women),
      and the frequency of osteopenia is 36.8% for men and 39.3% for women in Iran Accordingly, the
      prevention of osteopenia progression towards osteoporosis has been considered as an important
      issue in medicine. Bone is a dynamic tissue that is constantly being remodeled thus the
      equilibrium between bone formation and resorption done by simultaneously regulating
      osteoclasts and osteoblasts is important. Imbalance between bone deposition and resorption
      contributes to reducing bone mineral density and hence increasing the risk of osteoporosis

      Recently, new therapies have been focused on use of medicinal herbs, especially
      phytochemicals. Among phytochemicals, phytonutrients, and especially polyphenols, can act
      both on osteoblast and on osteoclast.

      Pine bark extract (oligopin) is a rich source of polyphenols that exerts strong antioxidant
      and anti-inflammatory activities. It has also beneficial effects on bone turnover based on in
      vitro studies and animal models. Investigators aimed to investigate the effects of oligopin
      on bone turnover markers and plasma and peripheral mononuclear cells oxidative stress in
      postmenopausal women with osteopenia in a double-blind randomized clinical trial.
      Participants are forty four women with osteopenia divided into two groups randomly (22,
      having oligopin, 150 mg, once daily, for 12 weeks). The 2nd group (22 women with osteopenia)
      receives the same amount of the placebo. At the first and the end of the study, blood sample
      are taken to measure in order to peripheral blood mononuclear cells isolation and plasma
      separation. The levels of bone alkaline phosphatase and carboxy terminal collagen type I in
      plasma oxidative stress markers such as total anti-oxidant capacity, malondialdehyde, and
      protein carbonyl were evaluated. Furthermore, oxidative stress will be evaluated in
      peripheral blood mononuclear cells by measurement of expression and activity of magnesium
      superoxide dismutase,catalase and Nuclear factor (erythroid-derived 2)-like 2.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Plasma Osteocalcin Concentration
time frame: up to third month after intervention
description: Osteocalcin levels in plasma
measure: Plasma Carboxyl terminal collagen type I Concentration
time frame: up to third month after intervention
description: Carboxyl terminal collagen type I in plasma
measure: Osteocalcin/Carboxyl terminal collagen type I ratio
time frame: up to third month after intervention
description: Osteocalcin/Carboxyl terminal collagen type I ratio
measure: MnSOD activity in peripheral blood mononuclear cells
time frame: Baseline and third month after intervention
description: MnSOD activity in peripheral blood mononuclear cells
measure: Catalase activity in peripheral blood mononuclear cells
time frame: Baseline and third month after intervention
description: Catalase activity in peripheral blood mono nuclear cells
measure: MnSOD mRNA expression peripheral blood mononuclear cells
time frame: Baseline and third month after intervention
description: MnSOD mRNA expression peripheral blood mononuclear cells
measure: Catalase mRNA expression peripheral blood mononuclear cells
time frame: Baseline and third month after intervention
description: Catalase mRNA expression peripheral blood mononuclear cells
measure: NrF2 mRNA expression peripheral blood mononuclear cells
time frame: Baseline and third month after intervention
description: NrF2 mRNA expression peripheral blood mononuclear cells
measure: Plasma Malondialdehide Concentration
time frame: Baseline and third month after intervention
description: Malondialdehide levels in plasma
measure: total antioxidant capacity
time frame: Baseline and third month after intervention
description: total antioxidant capacity in plasma
measure: protein carbonyl content
time frame: Baseline and third month after intervention
description: protein carbonyl content in plasma
measure: Plasma Total thiol concentration
time frame: Baseline and third month after intervention
description: Total thiol level in plasma
measure: Catalase activity in Plasma
time frame: Baseline and third month after intervention
description: Catalase activity in plasma
measure: MnSOD activity in Plasma
time frame: Baseline and third month after intervention
description: MnSOD activity in plasma
arm group label: postmenopausal osteopenic women receiveing Oligopin
arm group type: Experimental
description: postmenopausal osteopenic women receiving Oligopin ,150 mg ,once daily, 12 week
arm group label: postmenopausal osteopenic women receiving placebo
arm group type: Placebo Comparator
description: postmenopausal osteopenic women receiving placebo, 150 mg,once daily,12 weeks
intervention type: Drug
intervention name: Oligopin
description: Oligopin ,150 mg ,once daily, 12 week
arm group label: postmenopausal osteopenic women receiveing Oligopin
intervention type: Drug
intervention name: Placebo
description: Placebo,150 mg ,once daily, 12 week
arm group label: postmenopausal osteopenic women receiving placebo
criteria: 
gender: Female
minimum age: 50 Years
maximum age: 65 Years
healthy volunteers: No
facility: 
country: Iran, Islamic Republic of
responsible party type: Principal Investigator
investigator affiliation: Tehran University of Medical Sciences
investigator full name: Solaleh EmamGholi
investigator title: Principal Investigator
mesh term: Bone Diseases, Metabolic