<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/NCT02233257</url>
  </required_header>
  <id_info>
    <org_study_id>1401M47561</org_study_id>
    <nct_id>NCT02233257</nct_id>
  </id_info>
  <brief_title>Expanded Access for Lorenzo's Oil (GTO/GTE) in Adrenoleukodystrophy</brief_title>
  <official_title>Expanded Access for Lorenzo's Oil (GTO/GTE) in Adrenoleukodystrophy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Minnesota</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Minnesota</source>
  <brief_summary>
    <textblock>
      X-linked adrenoleukodystrophy (ALD) is a genetic disorder affecting the brain and adrenal&#xD;
      glands. Approximately one third of boys who are at risk will develop cerebral disease. Using&#xD;
      a specific diet and the compound Lorenzo's oil, it can be shown that very long chain fatty&#xD;
      acids may be lowered in the blood, but it is not known to what degree that may prevent the&#xD;
      onset of childhood disease.&#xD;
&#xD;
      This proposal makes available Lorenzo's oil to individuals with ALD, a life threatening&#xD;
      disorder for which there are presently no other therapies.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Expanded Access for Lorenzo's Oil in X-linked Adrenoleukodystrophy to Intermediate Size Group&#xD;
&#xD;
      Introduction/Rationale: A diet that consists predominantly of long-chain monounsaturated&#xD;
      fatty acids has been demonstrated to reduce the levels of very long chain fatty acids (VLCA)&#xD;
      in individuals with X-linked adrenoleukodystrophy (ALD). VLCFA are the primary biochemical&#xD;
      abnormality in this genetic disorder and have been implicated in the pathogenesis of the&#xD;
      cerebral disease. It has been demonstrated in an open study that reduction of VLCFA for more&#xD;
      than a year is protective for childhood cerebral disease.&#xD;
&#xD;
      The purpose of this expanded access proposal is to transition an open label study presently&#xD;
      ongoing in boys between the ages of 18 months and 13 years of age to an expanded access&#xD;
      study. The reason for this transition is lack of funding for the investigator to continue to&#xD;
      support this as a study. A study requires investigator involvement including the assistance&#xD;
      of research associates to monitor and track outcomes, perform neuropsychological assessments,&#xD;
      monitor adverse events, and coordinate periodic evaluations.&#xD;
&#xD;
      A move to expanded access would decentralize the coordination and monitoring of evaluations&#xD;
      which are clinically indicated even for participants who are not participating in a study.&#xD;
      This role would be undertaken by the treating physician.&#xD;
&#xD;
      Data collected in such an open study could serve as safety material for a later filing.&#xD;
&#xD;
      Study Population:&#xD;
&#xD;
        -  Males with X-linked adrenoleukodystrophy; see inclusion/exclusion criteria below.&#xD;
&#xD;
      Procedure:&#xD;
&#xD;
        1. Individuals who wish to obtain oil will submit clinical documentation of diagnosis to&#xD;
           Dr. Gerald Raymond. This will be either elevated very long chain fatty acids (VLCFA) or&#xD;
           DNA diagnosis of a mutation.&#xD;
&#xD;
        2. Identify a provider who will be responsible for the supervision of the diet. It is&#xD;
           suggested that this be an individual who is experienced in managing individuals on a&#xD;
           special diets such as a biochemical geneticist or neurologist with experience in ALD.&#xD;
&#xD;
        3. Studies required before prescription (It is important to emphasize that while many of&#xD;
           the following are performed solely for the use of Lorenzo's oil, the costs of these&#xD;
           investigations and consults will be the financial responsibility of the participants.)&#xD;
&#xD;
             1. Baseline VLCFA, complete blood count with platelets, and comprehensive metabolic&#xD;
                panel&#xD;
&#xD;
             2. Nutrition consult with a determination of daily calories. Thirty percent of&#xD;
                calories will be provided by lipids and 2/3 of these lipid calories will be&#xD;
                provided by long chain monounsaturated fatty acids (Lorenzo's oil). This&#xD;
                nutritional evaluation will include the following.&#xD;
&#xD;
           i. Present body parameters including weight, height, and BMI ii. Calculated daily&#xD;
           calories and other nutritional needs for growth. iii. Calculation of percent of diet as&#xD;
           lipids and amount of oil to be consumed daily iv. Instruction in diet restriction and&#xD;
           monitoring of said diet. v. Recommend supplements. vi. Instructions in providing diet&#xD;
           recall vii. Suggestions for maintaining and improving compliance. c. An MRI and adrenal&#xD;
           testing are clinically indicated and will be required as part of expanded access.&#xD;
&#xD;
        4. Clinical research forms (CRF) will be designed for the baseline and follow up&#xD;
           information for uniformity of documentation.&#xD;
&#xD;
        5. Upon receipt of this information, Dr. Raymond will provide an authorization of the&#xD;
           prescription to the supplier, Nutricia N.A.&#xD;
&#xD;
        6. Monitoring while receiving oil will consist of the following&#xD;
&#xD;
             1. VLCFA; Complete blood count (CBC), and Comprehensive metabolic panel every 3 months&#xD;
&#xD;
             2. Nutrition consult yearly.&#xD;
&#xD;
             3. Magnetic Resonance Imaging of the brain will be performed every 6-12 months&#xD;
&#xD;
             4. Appropriate monitoring of adrenal function.&#xD;
&#xD;
             5. CRFs' will be forwarded every three months for all active participants on a&#xD;
                January, April, July, October schedule&#xD;
&#xD;
             6. The identified provider will be responsible for providing this information to Dr.&#xD;
                Raymond's office. Failure to provide this information will result in withholding of&#xD;
                authorization and no dispensing of the product.&#xD;
&#xD;
             7. No more than 3 months' supply of the product will be authorized or shipped at a&#xD;
                time.&#xD;
&#xD;
             8. In the event of development of thrombocytopenia, Lorenzo's oil will be suspended&#xD;
                and glyceryl trioleate (GTO) substituted for one month and then reintroduced as&#xD;
                half dose of Lorenzo's oil followed by incremental increases as tolerated. We have&#xD;
                previously used 80,000 platelets as a lower limit and would recommend this as&#xD;
                providing an adequate margin of safety.&#xD;
&#xD;
        7. Adverse events will be tracked and if resulting in hospitalization or death will be&#xD;
           reported as required to the sponsor and FDA in the required period of time.&#xD;
&#xD;
      Otherwise all reported adverse events will be tabulated and reported in the yearly IND&#xD;
      report.&#xD;
&#xD;
      Adverse events will include conversion of normal MRIs to those demonstrating cerebral disease&#xD;
      and any interventions including bone marrow transplantation or gene therapy which are&#xD;
      presently the only options to halt cerebral disease.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>No longer available</overall_status>
  <study_type>Expanded Access</study_type>
  <condition>X-linked Adrenoleukodystrophy</condition>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lorenzo's Oil</intervention_name>
    <description>Oral use of Lorenzo's oil to lower very long chain fatty acids</description>
    <other_name>Glyceryl trierucate</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Males with X-linked adrenoleukodystrophy as determined by biochemical or genetic&#xD;
             determination.&#xD;
&#xD;
          -  Greater than 18 months of age through 18 years of age&#xD;
&#xD;
          -  Normal cerebral MRI at baseline.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Medical issues which preclude the administration of Lorenzo's oil&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Months</minimum_age>
    <maximum_age>18 Years</maximum_age>
  </eligibility>
  <overall_official>
    <last_name>Gerald V Raymond, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Minnesota</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Minnesota Medical Center</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>May 5, 2014</study_first_submitted>
  <study_first_submitted_qc>September 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 8, 2014</study_first_posted>
  <last_update_submitted>January 22, 2018</last_update_submitted>
  <last_update_submitted_qc>January 22, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 23, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Adrenoleukodystrophy</keyword>
  <keyword>Lorenzo's oil</keyword>
  <keyword>erucic acid</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adrenoleukodystrophy</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/NCT02233257
org study id: 1401M47561
nct id: NCT02233257
lead sponsor: 
X-linked adrenoleukodystrophy (ALD) is a genetic disorder affecting the brain and adrenal
      glands. Approximately one third of boys who are at risk will develop cerebral disease. Using
      a specific diet and the compound Lorenzo's oil, it can be shown that very long chain fatty
      acids may be lowered in the blood, but it is not known to what degree that may prevent the
      onset of childhood disease.

      This proposal makes available Lorenzo's oil to individuals with ALD, a life threatening
      disorder for which there are presently no other therapies.
Expanded Access for Lorenzo's Oil in X-linked Adrenoleukodystrophy to Intermediate Size Group

      Introduction/Rationale: A diet that consists predominantly of long-chain monounsaturated
      fatty acids has been demonstrated to reduce the levels of very long chain fatty acids (VLCA)
      in individuals with X-linked adrenoleukodystrophy (ALD). VLCFA are the primary biochemical
      abnormality in this genetic disorder and have been implicated in the pathogenesis of the
      cerebral disease. It has been demonstrated in an open study that reduction of VLCFA for more
      than a year is protective for childhood cerebral disease.

      The purpose of this expanded access proposal is to transition an open label study presently
      ongoing in boys between the ages of 18 months and 13 years of age to an expanded access
      study. The reason for this transition is lack of funding for the investigator to continue to
      support this as a study. A study requires investigator involvement including the assistance
      of research associates to monitor and track outcomes, perform neuropsychological assessments,
      monitor adverse events, and coordinate periodic evaluations.

      A move to expanded access would decentralize the coordination and monitoring of evaluations
      which are clinically indicated even for participants who are not participating in a study.
      This role would be undertaken by the treating physician.

      Data collected in such an open study could serve as safety material for a later filing.

      Study Population:

        -  Males with X-linked adrenoleukodystrophy; see inclusion/exclusion criteria below.

      Procedure:

        1. Individuals who wish to obtain oil will submit clinical documentation of diagnosis to
           Dr. Gerald Raymond. This will be either elevated very long chain fatty acids (VLCFA) or
           DNA diagnosis of a mutation.

        2. Identify a provider who will be responsible for the supervision of the diet. It is
           suggested that this be an individual who is experienced in managing individuals on a
           special diets such as a biochemical geneticist or neurologist with experience in ALD.

        3. Studies required before prescription (It is important to emphasize that while many of
           the following are performed solely for the use of Lorenzo's oil, the costs of these
           investigations and consults will be the financial responsibility of the participants.)

             1. Baseline VLCFA, complete blood count with platelets, and comprehensive metabolic
                panel

             2. Nutrition consult with a determination of daily calories. Thirty percent of
                calories will be provided by lipids and 2/3 of these lipid calories will be
                provided by long chain monounsaturated fatty acids (Lorenzo's oil). This
                nutritional evaluation will include the following.

           i. Present body parameters including weight, height, and BMI ii. Calculated daily
           calories and other nutritional needs for growth. iii. Calculation of percent of diet as
           lipids and amount of oil to be consumed daily iv. Instruction in diet restriction and
           monitoring of said diet. v. Recommend supplements. vi. Instructions in providing diet
           recall vii. Suggestions for maintaining and improving compliance. c. An MRI and adrenal
           testing are clinically indicated and will be required as part of expanded access.

        4. Clinical research forms (CRF) will be designed for the baseline and follow up
           information for uniformity of documentation.

        5. Upon receipt of this information, Dr. Raymond will provide an authorization of the
           prescription to the supplier, Nutricia N.A.

        6. Monitoring while receiving oil will consist of the following

             1. VLCFA; Complete blood count (CBC), and Comprehensive metabolic panel every 3 months

             2. Nutrition consult yearly.

             3. Magnetic Resonance Imaging of the brain will be performed every 6-12 months

             4. Appropriate monitoring of adrenal function.

             5. CRFs' will be forwarded every three months for all active participants on a
                January, April, July, October schedule

             6. The identified provider will be responsible for providing this information to Dr.
                Raymond's office. Failure to provide this information will result in withholding of
                authorization and no dispensing of the product.

             7. No more than 3 months' supply of the product will be authorized or shipped at a
                time.

             8. In the event of development of thrombocytopenia, Lorenzo's oil will be suspended
                and glyceryl trioleate (GTO) substituted for one month and then reintroduced as
                half dose of Lorenzo's oil followed by incremental increases as tolerated. We have
                previously used 80,000 platelets as a lower limit and would recommend this as
                providing an adequate margin of safety.

        7. Adverse events will be tracked and if resulting in hospitalization or death will be
           reported as required to the sponsor and FDA in the required period of time.

      Otherwise all reported adverse events will be tabulated and reported in the yearly IND
      report.

      Adverse events will include conversion of normal MRIs to those demonstrating cerebral disease
      and any interventions including bone marrow transplantation or gene therapy which are
      presently the only options to halt cerebral disease.
intervention type: Drug
intervention name: Lorenzo's Oil
description: Oral use of Lorenzo's oil to lower very long chain fatty acids
other name: Glyceryl trierucate
criteria: 
gender: Male
minimum age: 18 Months
maximum age: 18 Years
last name: Gerald V Raymond, MD
role: Principal Investigator
affiliation: University of Minnesota
facility: 
country: United States
responsible party type: Sponsor
mesh term: Adrenoleukodystrophy