<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/NCT03011203</url>
  </required_header>
  <id_info>
    <org_study_id>NL59081.042.16</org_study_id>
    <nct_id>NCT03011203</nct_id>
  </id_info>
  <brief_title>Acute Nutritional Ketosis in GSD IIIa</brief_title>
  <official_title>Acute Nutritional Ketosis and Exercise in Glycogen Storage Disease Type IIIa</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Medical Center Groningen</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of the Faroe Islands</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Oxford</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Stichting Stofwisselkracht</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Stichting Metakids</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Medical Center Groningen</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>
      The investigators will study if acute nutritional ketosis in adult GSD IIIa patients can&#xD;
      boost muscle mitochondrial function in vivo.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Glycogen Storage Disease type IIIa (GSD IIIa) is an inborn error of carbohydrate metabolism&#xD;
      caused by impaired glycogen debranching enzyme (GDE) activity. The ageing GSD IIIa cohort&#xD;
      shows that muscle involvement -despite dietary management- is a common disabling phenotype in&#xD;
      adulthood. Currently, no specific therapy has been established for muscle problems in adult&#xD;
      GSD IIIa patients.&#xD;
&#xD;
      However, it could be hypothesized that nutritional ketosis (NK) will be highly beneficial to&#xD;
      patients. Amongst others, ketone bodies could take on the role of primary energy source in&#xD;
      exercising muscle. Recently, acute NK in exercise was studied in humans. NK was found to&#xD;
      enhance muscle mitochondrial function in athletes.&#xD;
&#xD;
      The investigators will study if acute NK in adult GSD IIIa patients can boost muscle&#xD;
      mitochondrial function in vivo.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 10, 2017</start_date>
  <completion_date type="Actual">March 23, 2018</completion_date>
  <primary_completion_date type="Actual">March 23, 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>Crossover Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Description of in vivo energy and proton balance during exercise in MR scanner with and without ketone ester drink: steady-state intramuscular levels of glycogen, Pi, PCr and pH and kinetic rate constant of metabolic recovery.</measure>
    <time_frame>10 minutes; during in-magnet exercise test of session II and III.</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>time of individual desired workload</measure>
    <time_frame>through completion of the maximum exercise test (of approximately 12 minutes) during study session I.</time_frame>
    <description>#minutes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>completion of supine bicycling bout at desired workload in scanner</measure>
    <time_frame>10 min</time_frame>
    <description>(yes/no; if no, #minutes)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Muscle ultrasound density of the biceps, quadriceps, calf (gastrocnemius and/or soleus) and tibialis anterior muscles.</measure>
    <time_frame>Together with the muscle force examination this assessment will take 1.5 hour.</time_frame>
    <description>Will be performed during study session I by a neurologist.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Muscle force unilateral</measure>
    <time_frame>Together with the muscle ultrasound this assessment will take 1.5 hour.</time_frame>
    <description>Will be performed during study session I by a neurologist.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Subjective fatigue and muscle ache score</measure>
    <time_frame>after each exercise bout and 24 hours after exercise</time_frame>
    <description>scale 0-10</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>International Physical Activity Questionnaire</measure>
    <time_frame>This questionnaire will take 10 minutes to fill out. Participants will be asked to fill out the questionnaire one week before study session II and III</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Structural muscle parameters: fat infiltration.</measure>
    <time_frame>During the in-magnet exercise test of 10 minutes during session II and III</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in blood glucose levels</measure>
    <time_frame>Up to 7 samples will be taken during the 25 minutes exercise test (session II and III).</time_frame>
    <description>#1 and #2 at baseline, #3 after 10 min, #4 after 15 minutes, #5 at the start of bicycle exercise test inside scanner, #6 after 10 minutes of in-magnet exercise and #7 three hours post-exercise inside scanner.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood ketones level (β-hydroxybutyrate, acetoacetate).</measure>
    <time_frame>Up to 7 samples will be taken during the 25 minutes exercise test (session II and III).</time_frame>
    <description>#1 and #2 at baseline, #3 after 10 min, #4 after 15 minutes, #5 at the start of bicycle exercise test inside scanner, #6 after 10 minutes of in-magnet exercise and #7 three hours post-exercise inside scanner.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of blood pH</measure>
    <time_frame>Up to 7 samples will be taken during the 25 minutes exercise test (session II and III).</time_frame>
    <description>#1 and #2 at baseline, #3 after 10 min, #4 after 15 minutes, #5 at the start of bicycle exercise test inside scanner, #6 after 10 minutes of in-magnet exercise and #7 three hours post-exercise inside scanner.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood levels of free fatty acids</measure>
    <time_frame>Up to 7 samples will be taken during the 25 minutes exercise test (session II and III).</time_frame>
    <description>#1 and #2 at baseline, #3 after 10 min, #4 after 15 minutes, #5 at the start of bicycle exercise test inside scanner, #6 after 10 minutes of in-magnet exercise and #7 three hours post-exercise inside scanner.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood levels of insulin</measure>
    <time_frame>Up to 7 samples will be taken during the 25 minutes exercise test (session II and III).</time_frame>
    <description>#1 and #2 at baseline, #3 after 10 min, #4 after 15 minutes, #5 at the start of bicycle exercise test inside scanner, #6 after 10 minutes of in-magnet exercise and #7 three hours post-exercise inside scanner.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood levels of creatine kinase</measure>
    <time_frame>Up to 7 samples will be taken during the 25 minutes exercise test (session II and III).</time_frame>
    <description>#1 and #2 at baseline, #3 after 10 min, #4 after 15 minutes, #5 at the start of bicycle exercise test inside scanner, #6 after 10 minutes of in-magnet exercise and #7 three hours post-exercise inside scanner.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood levels of ammonia</measure>
    <time_frame>Up to 7 samples will be taken during the 25 minutes exercise test (session II and III).</time_frame>
    <description>#1 and #2 at baseline, #3 after 10 min, #4 after 15 minutes, #5 at the start of bicycle exercise test inside scanner, #6 after 10 minutes of in-magnet exercise and #7 three hours post-exercise inside scanner.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood levels of NT-proBNP</measure>
    <time_frame>Up to 7 samples will be taken during the 25 minutes exercise test (session II and III).</time_frame>
    <description>#1 and #2 at baseline, #3 after 10 min, #4 after 15 minutes, #5 at the start of bicycle exercise test inside scanner, #6 after 10 minutes of in-magnet exercise and #7 three hours post-exercise inside scanner.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood levels of lactate</measure>
    <time_frame>Up to 7 samples will be taken during the 25 minutes exercise test (session II and III).</time_frame>
    <description>#1 and #2 at baseline, #3 after 10 min, #4 after 15 minutes, #5 at the start of bicycle exercise test inside scanner, #6 after 10 minutes of in-magnet exercise and #7 three hours post-exercise inside scanner.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of urine levels of myoglobin, ketones, tetraglucoside</measure>
    <time_frame>Urine will be collected through study session II and III. A study session will take place from 8 am till 2 pm.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>optional: muscle metabolic profile (according to Cox et. al. 2016] of a muscle biopsy.</measure>
    <time_frame>This procedure takes 30 minutes each time and will be performed prior to and immediately post-exercise during study session II and III.</time_frame>
    <description>optional, on a patient-voluntary basis. If consent has been given a total of 4 muscle biopsies will be performed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>optional: individual phenotypic muscle properties (fiber type, mitochondrial density, capillary density</measure>
    <time_frame>This procedure takes 30 minutes each time and will be performed prior to and immediately post-exercise during study session II and III.</time_frame>
    <description>optional, on a patient-voluntary basis. If consent has been given a total of 4 muscle biopsies will be performed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Individual physical performance during exercise; VO2 and VCO2 dynamics.</measure>
    <time_frame>During session I; the maximum exercise test of approximately 12 minutes and during the exercise tests of 15 minutes outside the MR scanner at session II and III.</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Glycogen Storage Disease IIIA</condition>
  <arm_group>
    <arm_group_label>Ketone-ester drink</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral intake - physical exercise</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Carbohydrate drink</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Oral intake - physical exercise</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>physical exercise</intervention_name>
    <description>In session II and III participants will perform an exercise test on a bicycle inside and outside the MR scanner.</description>
    <arm_group_label>Carbohydrate drink</arm_group_label>
    <arm_group_label>Ketone-ester drink</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  GSD III confirmed with enzyme assay and/or AGL mutation analysis and GSD IIIa further&#xD;
             specified as deficient debranching enzyme activity in muscle or clinical and/or&#xD;
             biochemical signs of cardiac and/or skeletal muscular involvement.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  contraindications for MRI studies (assessed by standardised questionnaire)&#xD;
&#xD;
          -  inability to perform bicycle exercise.&#xD;
&#xD;
          -  intercurrent illness which may influence exercise tolerance (anemia, musculoskeletal&#xD;
             injury, or other undiagnosed illness under investigation).&#xD;
&#xD;
          -  known coronary artery disease, positive history for angina or cardiomyopathy.&#xD;
&#xD;
          -  insulin-dependent diabetes mellitus.&#xD;
&#xD;
          -  loss of, or an inability to give informed consent.&#xD;
&#xD;
          -  pregnancy or current breastfeeding.&#xD;
&#xD;
          -  any other cause which in the opinion of the investigators, may affect the&#xD;
             participant's ability to participate in the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>T.G.J. Derks, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Medical Center Groningen</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Groningen, UMC Groningen</name>
      <address>
        <city>Groningen</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <reference>
    <citation>Cox PJ, Kirk T, Ashmore T, Willerton K, Evans R, Smith A, Murray AJ, Stubbs B, West J, McLure SW, King MT, Dodd MS, Holloway C, Neubauer S, Drawer S, Veech RL, Griffin JL, Clarke K. Nutritional Ketosis Alters Fuel Preference and Thereby Endurance Performance in Athletes. Cell Metab. 2016 Aug 9;24(2):256-68. doi: 10.1016/j.cmet.2016.07.010. Epub 2016 Jul 27.</citation>
    <PMID>27475046</PMID>
  </reference>
  <reference>
    <citation>Diekman EF, Visser G, Schmitz JP, Nievelstein RA, de Sain-van der Velden M, Wardrop M, Van der Pol WL, Houten SM, van Riel NA, Takken T, Jeneson JA. Altered Energetics of Exercise Explain Risk of Rhabdomyolysis in Very Long-Chain Acyl-CoA Dehydrogenase Deficiency. PLoS One. 2016 Feb 16;11(2):e0147818. doi: 10.1371/journal.pone.0147818. eCollection 2016.</citation>
    <PMID>26881790</PMID>
  </reference>
  <reference>
    <citation>Sentner CP, Hoogeveen IJ, Weinstein DA, Santer R, Murphy E, McKiernan PJ, Steuerwald U, Beauchamp NJ, Taybert J, Laforet P, Petit FM, Hubert A, Labrune P, Smit GPA, Derks TGJ. Glycogen storage disease type III: diagnosis, genotype, management, clinical course and outcome. J Inherit Metab Dis. 2016 Sep;39(5):697-704. doi: 10.1007/s10545-016-9932-2. Epub 2016 Apr 22.</citation>
    <PMID>27106217</PMID>
  </reference>
  <reference>
    <citation>Verbeek RJ, Sentner CP, Smit GP, Maurits NM, Derks TG, van der Hoeven JH, Sival DA. Muscle Ultrasound in Patients with Glycogen Storage Disease Types I and III. Ultrasound Med Biol. 2016 Jan;42(1):133-42. doi: 10.1016/j.ultrasmedbio.2015.08.013. Epub 2015 Oct 3.</citation>
    <PMID>26437929</PMID>
  </reference>
  <reference>
    <citation>Preisler N, Laforet P, Madsen KL, Prahm KP, Hedermann G, Vissing CR, Galbo H, Vissing J. Skeletal muscle metabolism is impaired during exercise in glycogen storage disease type III. Neurology. 2015 Apr 28;84(17):1767-71. doi: 10.1212/WNL.0000000000001518. Epub 2015 Apr 1.</citation>
    <PMID>25832663</PMID>
  </reference>
  <verification_date>April 2018</verification_date>
  <study_first_submitted>December 22, 2016</study_first_submitted>
  <study_first_submitted_qc>January 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 5, 2017</study_first_posted>
  <last_update_submitted>April 30, 2018</last_update_submitted>
  <last_update_submitted_qc>April 30, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">May 1, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University Medical Center Groningen</investigator_affiliation>
    <investigator_full_name>Terry G.J. Derks, MD, PhD</investigator_full_name>
    <investigator_title>Pediatrician consultant metabolic medicine</investigator_title>
  </responsible_party>
  <keyword>glycogen storage disease type IIIa</keyword>
  <keyword>exercise</keyword>
  <keyword>ketone esters</keyword>
  <keyword>magnetic resonance spectroscopy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glycogen Storage Disease</mesh_term>
    <mesh_term>Metabolic Diseases</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/NCT03011203
org study id: NL59081.042.16
nct id: NCT03011203
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The investigators will study if acute nutritional ketosis in adult GSD IIIa patients can
      boost muscle mitochondrial function in vivo.
Glycogen Storage Disease type IIIa (GSD IIIa) is an inborn error of carbohydrate metabolism
      caused by impaired glycogen debranching enzyme (GDE) activity. The ageing GSD IIIa cohort
      shows that muscle involvement -despite dietary management- is a common disabling phenotype in
      adulthood. Currently, no specific therapy has been established for muscle problems in adult
      GSD IIIa patients.

      However, it could be hypothesized that nutritional ketosis (NK) will be highly beneficial to
      patients. Amongst others, ketone bodies could take on the role of primary energy source in
      exercising muscle. Recently, acute NK in exercise was studied in humans. NK was found to
      enhance muscle mitochondrial function in athletes.

      The investigators will study if acute NK in adult GSD IIIa patients can boost muscle
      mitochondrial function in vivo.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Other
masking: Double (Participant, Outcomes Assessor)
measure: Description of in vivo energy and proton balance during exercise in MR scanner with and without ketone ester drink: steady-state intramuscular levels of glycogen, Pi, PCr and pH and kinetic rate constant of metabolic recovery.
time frame: 10 minutes; during in-magnet exercise test of session II and III.
measure: time of individual desired workload
time frame: through completion of the maximum exercise test (of approximately 12 minutes) during study session I.
description: #minutes
measure: completion of supine bicycling bout at desired workload in scanner
time frame: 10 min
description: (yes/no; if no, #minutes)
measure: Muscle ultrasound density of the biceps, quadriceps, calf (gastrocnemius and/or soleus) and tibialis anterior muscles.
time frame: Together with the muscle force examination this assessment will take 1.5 hour.
description: Will be performed during study session I by a neurologist.
measure: Muscle force unilateral
time frame: Together with the muscle ultrasound this assessment will take 1.5 hour.
description: Will be performed during study session I by a neurologist.
measure: Subjective fatigue and muscle ache score
time frame: after each exercise bout and 24 hours after exercise
description: scale 0-10
measure: International Physical Activity Questionnaire
time frame: This questionnaire will take 10 minutes to fill out. Participants will be asked to fill out the questionnaire one week before study session II and III
measure: Structural muscle parameters: fat infiltration.
time frame: During the in-magnet exercise test of 10 minutes during session II and III
measure: Change in blood glucose levels
time frame: Up to 7 samples will be taken during the 25 minutes exercise test (session II and III).
description: #1 and #2 at baseline, #3 after 10 min, #4 after 15 minutes, #5 at the start of bicycle exercise test inside scanner, #6 after 10 minutes of in-magnet exercise and #7 three hours post-exercise inside scanner.
measure: Blood ketones level (β-hydroxybutyrate, acetoacetate).
time frame: Up to 7 samples will be taken during the 25 minutes exercise test (session II and III).
description: #1 and #2 at baseline, #3 after 10 min, #4 after 15 minutes, #5 at the start of bicycle exercise test inside scanner, #6 after 10 minutes of in-magnet exercise and #7 three hours post-exercise inside scanner.
measure: Change of blood pH
time frame: Up to 7 samples will be taken during the 25 minutes exercise test (session II and III).
description: #1 and #2 at baseline, #3 after 10 min, #4 after 15 minutes, #5 at the start of bicycle exercise test inside scanner, #6 after 10 minutes of in-magnet exercise and #7 three hours post-exercise inside scanner.
measure: Blood levels of free fatty acids
time frame: Up to 7 samples will be taken during the 25 minutes exercise test (session II and III).
description: #1 and #2 at baseline, #3 after 10 min, #4 after 15 minutes, #5 at the start of bicycle exercise test inside scanner, #6 after 10 minutes of in-magnet exercise and #7 three hours post-exercise inside scanner.
measure: Blood levels of insulin
time frame: Up to 7 samples will be taken during the 25 minutes exercise test (session II and III).
description: #1 and #2 at baseline, #3 after 10 min, #4 after 15 minutes, #5 at the start of bicycle exercise test inside scanner, #6 after 10 minutes of in-magnet exercise and #7 three hours post-exercise inside scanner.
measure: Blood levels of creatine kinase
time frame: Up to 7 samples will be taken during the 25 minutes exercise test (session II and III).
description: #1 and #2 at baseline, #3 after 10 min, #4 after 15 minutes, #5 at the start of bicycle exercise test inside scanner, #6 after 10 minutes of in-magnet exercise and #7 three hours post-exercise inside scanner.
measure: Blood levels of ammonia
time frame: Up to 7 samples will be taken during the 25 minutes exercise test (session II and III).
description: #1 and #2 at baseline, #3 after 10 min, #4 after 15 minutes, #5 at the start of bicycle exercise test inside scanner, #6 after 10 minutes of in-magnet exercise and #7 three hours post-exercise inside scanner.
measure: Blood levels of NT-proBNP
time frame: Up to 7 samples will be taken during the 25 minutes exercise test (session II and III).
description: #1 and #2 at baseline, #3 after 10 min, #4 after 15 minutes, #5 at the start of bicycle exercise test inside scanner, #6 after 10 minutes of in-magnet exercise and #7 three hours post-exercise inside scanner.
measure: Blood levels of lactate
time frame: Up to 7 samples will be taken during the 25 minutes exercise test (session II and III).
description: #1 and #2 at baseline, #3 after 10 min, #4 after 15 minutes, #5 at the start of bicycle exercise test inside scanner, #6 after 10 minutes of in-magnet exercise and #7 three hours post-exercise inside scanner.
measure: Change of urine levels of myoglobin, ketones, tetraglucoside
time frame: Urine will be collected through study session II and III. A study session will take place from 8 am till 2 pm.
measure: optional: muscle metabolic profile (according to Cox et. al. 2016] of a muscle biopsy.
time frame: This procedure takes 30 minutes each time and will be performed prior to and immediately post-exercise during study session II and III.
description: optional, on a patient-voluntary basis. If consent has been given a total of 4 muscle biopsies will be performed.
measure: optional: individual phenotypic muscle properties (fiber type, mitochondrial density, capillary density
time frame: This procedure takes 30 minutes each time and will be performed prior to and immediately post-exercise during study session II and III.
description: optional, on a patient-voluntary basis. If consent has been given a total of 4 muscle biopsies will be performed.
measure: Individual physical performance during exercise; VO2 and VCO2 dynamics.
time frame: During session I; the maximum exercise test of approximately 12 minutes and during the exercise tests of 15 minutes outside the MR scanner at session II and III.
arm group label: Ketone-ester drink
arm group type: Experimental
description: Oral intake - physical exercise
arm group label: Carbohydrate drink
arm group type: Active Comparator
description: Oral intake - physical exercise
intervention type: Other
intervention name: physical exercise
description: In session II and III participants will perform an exercise test on a bicycle inside and outside the MR scanner.
arm group label: Carbohydrate drink
arm group label: Ketone-ester drink
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: T.G.J. Derks, MD PhD
role: Principal Investigator
affiliation: University Medical Center Groningen
facility: 
country: Netherlands
citation: Cox PJ, Kirk T, Ashmore T, Willerton K, Evans R, Smith A, Murray AJ, Stubbs B, West J, McLure SW, King MT, Dodd MS, Holloway C, Neubauer S, Drawer S, Veech RL, Griffin JL, Clarke K. Nutritional Ketosis Alters Fuel Preference and Thereby Endurance Performance in Athletes. Cell Metab. 2016 Aug 9;24(2):256-68. doi: 10.1016/j.cmet.2016.07.010. Epub 2016 Jul 27.
PMID: 27475046
citation: Diekman EF, Visser G, Schmitz JP, Nievelstein RA, de Sain-van der Velden M, Wardrop M, Van der Pol WL, Houten SM, van Riel NA, Takken T, Jeneson JA. Altered Energetics of Exercise Explain Risk of Rhabdomyolysis in Very Long-Chain Acyl-CoA Dehydrogenase Deficiency. PLoS One. 2016 Feb 16;11(2):e0147818. doi: 10.1371/journal.pone.0147818. eCollection 2016.
PMID: 26881790
citation: Sentner CP, Hoogeveen IJ, Weinstein DA, Santer R, Murphy E, McKiernan PJ, Steuerwald U, Beauchamp NJ, Taybert J, Laforet P, Petit FM, Hubert A, Labrune P, Smit GPA, Derks TGJ. Glycogen storage disease type III: diagnosis, genotype, management, clinical course and outcome. J Inherit Metab Dis. 2016 Sep;39(5):697-704. doi: 10.1007/s10545-016-9932-2. Epub 2016 Apr 22.
PMID: 27106217
citation: Verbeek RJ, Sentner CP, Smit GP, Maurits NM, Derks TG, van der Hoeven JH, Sival DA. Muscle Ultrasound in Patients with Glycogen Storage Disease Types I and III. Ultrasound Med Biol. 2016 Jan;42(1):133-42. doi: 10.1016/j.ultrasmedbio.2015.08.013. Epub 2015 Oct 3.
PMID: 26437929
citation: Preisler N, Laforet P, Madsen KL, Prahm KP, Hedermann G, Vissing CR, Galbo H, Vissing J. Skeletal muscle metabolism is impaired during exercise in glycogen storage disease type III. Neurology. 2015 Apr 28;84(17):1767-71. doi: 10.1212/WNL.0000000000001518. Epub 2015 Apr 1.
PMID: 25832663
responsible party type: Principal Investigator
investigator affiliation: University Medical Center Groningen
investigator full name: Terry G.J. Derks, MD, PhD
investigator title: Pediatrician consultant metabolic medicine
mesh term: Glycogen Storage Disease
mesh term: Metabolic Diseases
sharing ipd: Undecided