<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/NCT03043690</url>
  </required_header>
  <id_info>
    <org_study_id>AMSUCC2</org_study_id>
    <nct_id>NCT03043690</nct_id>
  </id_info>
  <brief_title>A Pooled Analysis of the Data From Two Studies of Ammonium Succinate for Menopausal Symptoms</brief_title>
  <official_title>Clinical Efficacy of an Ammonium Succinate-based Dietary Supplement in Women With Menopausal Symptoms: a Pooled Analysis of the Data From Two Randomized, Multicenter, Double-blinded Placebo-controlled Clinical Trials.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>I.M. Sechenov First Moscow State Medical University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>I.M. Sechenov First Moscow State Medical 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>
      This study is a pooled statistical analysis of the data from 2 studies concerning efficacy of&#xD;
      ammonium-succinate based dietary supplement. In both studies group 1 took the&#xD;
      ammonium-succinate based dietary supplement and the group 2 took placebo.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Both studies were conducted previously and were randomized, double-blind and&#xD;
      placebo-controlled. They followed very similar protocols, were of nearly identical design,&#xD;
      had common inclusion and exclusion criteria. Both studies achieved statistical significance&#xD;
      for ammonium succinate-based dietary supplement on most of pre-specified endpoints of Greene&#xD;
      Climacteric Scale symptoms severity reduction at week 12. Nevertheless, some minor variation&#xD;
      in the patient population, both within the studies (e.g., between different centres, as well&#xD;
      as seasonal variability) and between the studies can be expected.&#xD;
&#xD;
      Naturally occuring estrogen deficiency over the course of the menopausal transition and&#xD;
      postmenopause causes hot flushes and other psychosomatic and vasomotor symptoms. Menopausal&#xD;
      hormone therapy is a method of choice, however in many cases it is contraindicated or&#xD;
      unacceptable for other reasons. Many alternatives exist, generally acting via estrogen&#xD;
      receptors (ER). The dietary supplement tested in the aforementioned studies contains ammonium&#xD;
      succinate, which does not bind to ER, instead acting by supporting the Krebs cycle. It does&#xD;
      not have phytoestrogenic ingredients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 11, 2017</start_date>
  <completion_date type="Actual">May 30, 2017</completion_date>
  <primary_completion_date type="Actual">May 3, 2017</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Other</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>&quot;Heart beating quickly and strongly&quot; symptom (Greene Climacteric Scale)</measure>
    <time_frame>Week 12</time_frame>
    <description>Statistically significant reduction in designated symptom severity, compared between arms</description>
  </primary_outcome>
  <primary_outcome>
    <measure>&quot;Feeling tense or nervous&quot; symptom (Greene Climacteric Scale)</measure>
    <time_frame>Week 12</time_frame>
    <description>Statistically significant reduction in designated symptom severity, compared between arms</description>
  </primary_outcome>
  <primary_outcome>
    <measure>&quot;Difficulty in sleeping&quot; symptom (Greene Climacteric Scale)</measure>
    <time_frame>Week 12</time_frame>
    <description>Statistically significant reduction in designated symptom severity, compared between arms</description>
  </primary_outcome>
  <primary_outcome>
    <measure>&quot;Excitable&quot; symptom (Greene Climacteric Scale)</measure>
    <time_frame>Week 12</time_frame>
    <description>Statistically significant reduction in designated symptom severity, compared between arms</description>
  </primary_outcome>
  <primary_outcome>
    <measure>&quot;Attacks of panic&quot; symptom (Greene Climacteric Scale)</measure>
    <time_frame>Week 12</time_frame>
    <description>Statistically significant reduction in designated symptom severity, compared between arms</description>
  </primary_outcome>
  <primary_outcome>
    <measure>&quot;Difficulty in concentrating&quot; symptom (Greene Climacteric Scale)</measure>
    <time_frame>Week 12</time_frame>
    <description>Statistically significant reduction in designated symptom severity, compared between arms</description>
  </primary_outcome>
  <primary_outcome>
    <measure>&quot;Feeling tired or lacking in energy&quot; symptom (Greene Climacteric Scale)</measure>
    <time_frame>Week 12</time_frame>
    <description>Statistically significant reduction in designated symptom severity, compared between arms</description>
  </primary_outcome>
  <primary_outcome>
    <measure>&quot;Loss of interest in most things&quot; symptom (Greene Climacteric Scale)</measure>
    <time_frame>Week 12</time_frame>
    <description>Statistically significant reduction in designated symptom severity, compared between arms</description>
  </primary_outcome>
  <primary_outcome>
    <measure>&quot;Feeling unhappy or depressed&quot; symptom (Greene Climacteric Scale)</measure>
    <time_frame>Week 12</time_frame>
    <description>Statistically significant reduction in designated symptom severity, compared between arms</description>
  </primary_outcome>
  <primary_outcome>
    <measure>&quot;Crying spells&quot; symptom (Greene Climacteric Scale)</measure>
    <time_frame>Week 12</time_frame>
    <description>Statistically significant reduction in designated symptom severity, compared between arms</description>
  </primary_outcome>
  <primary_outcome>
    <measure>&quot;Irritability&quot; symptom (Greene Climacteric Scale)</measure>
    <time_frame>Week 12</time_frame>
    <description>Statistically significant reduction in designated symptom severity, compared between arms</description>
  </primary_outcome>
  <primary_outcome>
    <measure>&quot;Feeling dizzy or faint&quot; symptom (Greene Climacteric Scale)</measure>
    <time_frame>Week 12</time_frame>
    <description>Statistically significant reduction in designated symptom severity, compared between arms</description>
  </primary_outcome>
  <primary_outcome>
    <measure>&quot;Pressure or tightness in head or body&quot; symptom (Greene Climacteric Scale)</measure>
    <time_frame>Week 12</time_frame>
    <description>Statistically significant reduction in designated symptom severity, compared between arms</description>
  </primary_outcome>
  <primary_outcome>
    <measure>&quot;Parts of body feeling numb or tingling&quot; symptom (Greene Climacteric Scale)</measure>
    <time_frame>Week 12</time_frame>
    <description>Statistically significant reduction in designated symptom severity, compared between arms</description>
  </primary_outcome>
  <primary_outcome>
    <measure>&quot;Headaches&quot; symptom (Greene Climacteric Scale)</measure>
    <time_frame>Week 12</time_frame>
    <description>Statistically significant reduction in designated symptom severity, compared between arms</description>
  </primary_outcome>
  <primary_outcome>
    <measure>&quot;Muscle or joint pains&quot; symptom (Greene Climacteric Scale)</measure>
    <time_frame>Week 12</time_frame>
    <description>Statistically significant reduction in designated symptom severity, compared between arms</description>
  </primary_outcome>
  <primary_outcome>
    <measure>&quot;Loss of feeling in hands or feet&quot; symptom (Greene Climacteric Scale)</measure>
    <time_frame>Week 12</time_frame>
    <description>Statistically significant reduction in designated symptom severity, compared between arms</description>
  </primary_outcome>
  <primary_outcome>
    <measure>&quot;Breathing difficulties&quot; symptom (Greene Climacteric Scale)</measure>
    <time_frame>Week 12</time_frame>
    <description>Statistically significant reduction in designated symptom severity, compared between arms</description>
  </primary_outcome>
  <primary_outcome>
    <measure>&quot;Hot flushes&quot; symptom (Greene Climacteric Scale)</measure>
    <time_frame>Week 12</time_frame>
    <description>Statistically significant reduction in designated symptom severity, compared between arms</description>
  </primary_outcome>
  <primary_outcome>
    <measure>&quot;Sweating at night&quot; symptom (Greene Climacteric Scale)</measure>
    <time_frame>Week 12</time_frame>
    <description>Statistically significant reduction in designated symptom severity, compared between arms</description>
  </primary_outcome>
  <primary_outcome>
    <measure>&quot;Loss of interest in sex&quot; symptom (Greene Climacteric Scale)</measure>
    <time_frame>Week 12</time_frame>
    <description>Statistically significant reduction in designated symptom severity, compared between arms</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Spilberger-Hanin (Situational anxiety)</measure>
    <time_frame>Week 12</time_frame>
    <description>The decrease of situational anxiety, measured as statistically significant reduction of the score in corresponding subscale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Spilberger-Hanin (Personal anxiety)</measure>
    <time_frame>Week 12</time_frame>
    <description>The decrease of personal anxiety, measured as statistically significant reduction of the score in corresponding subscale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Spilberger-Hanin (Actual anxiety)</measure>
    <time_frame>Week 12</time_frame>
    <description>The decrease of actual anxiety, measured as statistically significant reduction of the score in corresponding subscale. Actual anxiety as a sum of situational and personal anxiety scores was introduced by Hanin in his modification of original State-Trait Anxiety Inventory.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">227</enrollment>
  <condition>Menopause Related Conditions</condition>
  <arm_group>
    <arm_group_label>Ammonium succinate</arm_group_label>
    <description>Patients in main pooled study group received 2 capsules of ammonium succinate-based dietary supplement (one white, 200 mg, and one orange, 200 mg), once a day, in the morning with a meal, for 90 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <description>Patients in placebo study group received 2 capsules of ammonium succinate-based dietary supplement (one white, 200 mg, and one orange, 200 mg), once a day, in the morning with a meal, for 90 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Ammonium succinate</intervention_name>
    <description>2 capsules of ammonium succinate-based dietary supplement (one white, 200 mg, and one orange, 200 mg), once a day, in the morning with a meal, for 90 days.</description>
    <arm_group_label>Ammonium succinate</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>2 capsules of ammonium succinate-based dietary supplement (one white, 200 mg, and one orange, 200 mg), once a day, in the morning with a meal, for 90 days.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Both studies chosen for pooled analysis recruited women with vasomotor and psychosomatic&#xD;
        complaints, in the late phase of the menopausal transition and postmenopause according to&#xD;
        the Stages of Reproductive Aging Workshop +10 classification.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  vasomotor and psychosomatic complaints&#xD;
&#xD;
          -  ability to comply to study protocol&#xD;
&#xD;
          -  signed informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  cancer (current or prior, based on medical history)&#xD;
&#xD;
          -  conditions requiring planned hospitalization in the next 6 months;&#xD;
&#xD;
          -  endocrine diseases with abnormal hormonal secretion (hypercorticism,&#xD;
             hyperprplactinemia, hypersomatotropism, thyroid disorders et c.);&#xD;
&#xD;
          -  any surgeries within 1 year of the screening;&#xD;
&#xD;
          -  hormone therapy within 6 months of the screening;&#xD;
&#xD;
          -  psychiatric diseases;&#xD;
&#xD;
          -  diabetes mellitus;&#xD;
&#xD;
          -  taking other supplements or medications that may affect the climacteric syndrome&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>42 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Irina V Kuznetsova</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sechenov First Moscow Medical University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sechenov First Moscow Medical University</name>
      <address>
        <city>Moscow</city>
        <zip>119991</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Russian Federation</country>
  </location_countries>
  <reference>
    <citation>Radzinskii VE, Kuznetsova IV, Uspenskaya YB, Repina NB, Gusak YK, Zubova OM, Burchakov DI, Osmakova AA. Treatment of climacteric symptoms with an ammonium succinate-based dietary supplement: a randomized, double-blind, placebo-controlled trial. Gynecol Endocrinol. 2016 Oct;32(sup2):64-68. doi: 10.1080/09513590.2016.1232686.</citation>
    <PMID>27759458</PMID>
  </reference>
  <reference>
    <citation>Harlow SD, Gass M, Hall JE, Lobo R, Maki P, Rebar RW, Sherman S, Sluss PM, de Villiers TJ; STRAW 10 Collaborative Group. Executive summary of the Stages of Reproductive Aging Workshop + 10: addressing the unfinished agenda of staging reproductive aging. Menopause. 2012 Apr;19(4):387-95. doi: 10.1097/gme.0b013e31824d8f40.</citation>
    <PMID>22343510</PMID>
  </reference>
  <reference>
    <citation>Greene JG. Constructing a standard climacteric scale. Maturitas. 2008 Sep-Oct;61(1-2):78-84. doi: 10.1016/j.maturitas.2008.09.011.</citation>
    <PMID>19434881</PMID>
  </reference>
  <verification_date>February 2017</verification_date>
  <study_first_submitted>February 2, 2017</study_first_submitted>
  <study_first_submitted_qc>February 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 6, 2017</study_first_posted>
  <last_update_submitted>October 18, 2017</last_update_submitted>
  <last_update_submitted_qc>October 18, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 20, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>I.M. Sechenov First Moscow State Medical University</investigator_affiliation>
    <investigator_full_name>Kuznetsova Irina</investigator_full_name>
    <investigator_title>Senior Research Fellow</investigator_title>
  </responsible_party>
  <keyword>menopause</keyword>
  <keyword>ammonium succinate</keyword>
  <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/NCT03043690
org study id: AMSUCC2
nct id: NCT03043690
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study is a pooled statistical analysis of the data from 2 studies concerning efficacy of
      ammonium-succinate based dietary supplement. In both studies group 1 took the
      ammonium-succinate based dietary supplement and the group 2 took placebo.
Both studies were conducted previously and were randomized, double-blind and
      placebo-controlled. They followed very similar protocols, were of nearly identical design,
      had common inclusion and exclusion criteria. Both studies achieved statistical significance
      for ammonium succinate-based dietary supplement on most of pre-specified endpoints of Greene
      Climacteric Scale symptoms severity reduction at week 12. Nevertheless, some minor variation
      in the patient population, both within the studies (e.g., between different centres, as well
      as seasonal variability) and between the studies can be expected.

      Naturally occuring estrogen deficiency over the course of the menopausal transition and
      postmenopause causes hot flushes and other psychosomatic and vasomotor symptoms. Menopausal
      hormone therapy is a method of choice, however in many cases it is contraindicated or
      unacceptable for other reasons. Many alternatives exist, generally acting via estrogen
      receptors (ER). The dietary supplement tested in the aforementioned studies contains ammonium
      succinate, which does not bind to ER, instead acting by supporting the Krebs cycle. It does
      not have phytoestrogenic ingredients.
observational model: Other
time perspective: Retrospective
measure: "Heart beating quickly and strongly" symptom (Greene Climacteric Scale)
time frame: Week 12
description: Statistically significant reduction in designated symptom severity, compared between arms
measure: "Feeling tense or nervous" symptom (Greene Climacteric Scale)
time frame: Week 12
description: Statistically significant reduction in designated symptom severity, compared between arms
measure: "Difficulty in sleeping" symptom (Greene Climacteric Scale)
time frame: Week 12
description: Statistically significant reduction in designated symptom severity, compared between arms
measure: "Excitable" symptom (Greene Climacteric Scale)
time frame: Week 12
description: Statistically significant reduction in designated symptom severity, compared between arms
measure: "Attacks of panic" symptom (Greene Climacteric Scale)
time frame: Week 12
description: Statistically significant reduction in designated symptom severity, compared between arms
measure: "Difficulty in concentrating" symptom (Greene Climacteric Scale)
time frame: Week 12
description: Statistically significant reduction in designated symptom severity, compared between arms
measure: "Feeling tired or lacking in energy" symptom (Greene Climacteric Scale)
time frame: Week 12
description: Statistically significant reduction in designated symptom severity, compared between arms
measure: "Loss of interest in most things" symptom (Greene Climacteric Scale)
time frame: Week 12
description: Statistically significant reduction in designated symptom severity, compared between arms
measure: "Feeling unhappy or depressed" symptom (Greene Climacteric Scale)
time frame: Week 12
description: Statistically significant reduction in designated symptom severity, compared between arms
measure: "Crying spells" symptom (Greene Climacteric Scale)
time frame: Week 12
description: Statistically significant reduction in designated symptom severity, compared between arms
measure: "Irritability" symptom (Greene Climacteric Scale)
time frame: Week 12
description: Statistically significant reduction in designated symptom severity, compared between arms
measure: "Feeling dizzy or faint" symptom (Greene Climacteric Scale)
time frame: Week 12
description: Statistically significant reduction in designated symptom severity, compared between arms
measure: "Pressure or tightness in head or body" symptom (Greene Climacteric Scale)
time frame: Week 12
description: Statistically significant reduction in designated symptom severity, compared between arms
measure: "Parts of body feeling numb or tingling" symptom (Greene Climacteric Scale)
time frame: Week 12
description: Statistically significant reduction in designated symptom severity, compared between arms
measure: "Headaches" symptom (Greene Climacteric Scale)
time frame: Week 12
description: Statistically significant reduction in designated symptom severity, compared between arms
measure: "Muscle or joint pains" symptom (Greene Climacteric Scale)
time frame: Week 12
description: Statistically significant reduction in designated symptom severity, compared between arms
measure: "Loss of feeling in hands or feet" symptom (Greene Climacteric Scale)
time frame: Week 12
description: Statistically significant reduction in designated symptom severity, compared between arms
measure: "Breathing difficulties" symptom (Greene Climacteric Scale)
time frame: Week 12
description: Statistically significant reduction in designated symptom severity, compared between arms
measure: "Hot flushes" symptom (Greene Climacteric Scale)
time frame: Week 12
description: Statistically significant reduction in designated symptom severity, compared between arms
measure: "Sweating at night" symptom (Greene Climacteric Scale)
time frame: Week 12
description: Statistically significant reduction in designated symptom severity, compared between arms
measure: "Loss of interest in sex" symptom (Greene Climacteric Scale)
time frame: Week 12
description: Statistically significant reduction in designated symptom severity, compared between arms
measure: Spilberger-Hanin (Situational anxiety)
time frame: Week 12
description: The decrease of situational anxiety, measured as statistically significant reduction of the score in corresponding subscale
measure: Spilberger-Hanin (Personal anxiety)
time frame: Week 12
description: The decrease of personal anxiety, measured as statistically significant reduction of the score in corresponding subscale
measure: Spilberger-Hanin (Actual anxiety)
time frame: Week 12
description: The decrease of actual anxiety, measured as statistically significant reduction of the score in corresponding subscale. Actual anxiety as a sum of situational and personal anxiety scores was introduced by Hanin in his modification of original State-Trait Anxiety Inventory.
arm group label: Ammonium succinate
description: Patients in main pooled study group received 2 capsules of ammonium succinate-based dietary supplement (one white, 200 mg, and one orange, 200 mg), once a day, in the morning with a meal, for 90 days.
arm group label: Placebo
description: Patients in placebo study group received 2 capsules of ammonium succinate-based dietary supplement (one white, 200 mg, and one orange, 200 mg), once a day, in the morning with a meal, for 90 days.
intervention type: Dietary Supplement
intervention name: Ammonium succinate
description: 2 capsules of ammonium succinate-based dietary supplement (one white, 200 mg, and one orange, 200 mg), once a day, in the morning with a meal, for 90 days.
arm group label: Ammonium succinate
intervention type: Other
intervention name: Placebo
description: 2 capsules of ammonium succinate-based dietary supplement (one white, 200 mg, and one orange, 200 mg), once a day, in the morning with a meal, for 90 days.
arm group label: Placebo
study pop: 
sampling method: Probability Sample
criteria: 
gender: Female
minimum age: 42 Years
maximum age: 60 Years
healthy volunteers: No
last name: Irina V Kuznetsova
role: Principal Investigator
affiliation: Sechenov First Moscow Medical University
facility: 
country: Russian Federation
citation: Radzinskii VE, Kuznetsova IV, Uspenskaya YB, Repina NB, Gusak YK, Zubova OM, Burchakov DI, Osmakova AA. Treatment of climacteric symptoms with an ammonium succinate-based dietary supplement: a randomized, double-blind, placebo-controlled trial. Gynecol Endocrinol. 2016 Oct;32(sup2):64-68. doi: 10.1080/09513590.2016.1232686.
PMID: 27759458
citation: Harlow SD, Gass M, Hall JE, Lobo R, Maki P, Rebar RW, Sherman S, Sluss PM, de Villiers TJ; STRAW 10 Collaborative Group. Executive summary of the Stages of Reproductive Aging Workshop + 10: addressing the unfinished agenda of staging reproductive aging. Menopause. 2012 Apr;19(4):387-95. doi: 10.1097/gme.0b013e31824d8f40.
PMID: 22343510
citation: Greene JG. Constructing a standard climacteric scale. Maturitas. 2008 Sep-Oct;61(1-2):78-84. doi: 10.1016/j.maturitas.2008.09.011.
PMID: 19434881
responsible party type: Principal Investigator
investigator affiliation: I.M. Sechenov First Moscow State Medical University
investigator full name: Kuznetsova Irina
investigator title: Senior Research Fellow
sharing ipd: No