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出境医 / 临床实验 / Fat and Glucose Metabolism in Fed and Fasted State in Patients With Low Skeletal Muscle Mass

Fat and Glucose Metabolism in Fed and Fasted State in Patients With Low Skeletal Muscle Mass

Study Description
Brief Summary:
In a study from 2003 the investigators showed that adult patients with very low skeletal muscle mass (spinal muscular atrophy (SMA) type II, Duchenne muscular dystrophy, congenital muscular dystrophy) are prone to develop hypoglycemia during prolonged fasting. Since then case reports have described the same phenomenon with hypoglycemia and metabolic crises in children with low skeletal muscle mass provoked by infection, fasting and surgery. Pathophysiological mechanisms of metabolism have never been investigated in adults or children with SMA II. Thus the investigators studied fat and glucose metabolism during prolonged fasting in patients with SMA II and LAMA 2 and compared results to those found in healthy controls.

Condition or disease Intervention/treatment Phase
Spinal Muscular Atrophy Merosin Deficient Congenital Muscular Dystrophy Other: Fasting Not Applicable

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Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Fedt og Sukkerstofskiftet Under Faste Hos Patienter Med Lav Muskelmasse.
Actual Study Start Date : May 29, 2017
Actual Primary Completion Date : November 30, 2017
Actual Study Completion Date : November 30, 2017
Arms and Interventions
Arm Intervention/treatment
Experimental: Fasting Other: Fasting
Fasting for 24 hours or until hypoglycemia (blood glucose < 3mmol/L) or symptoms of hypoglycemia

Outcome Measures
Primary Outcome Measures :
  1. Change in fat metabolisms from fed to fasted state [ Time Frame: 24 hours ]
    Using indirect calorimetri and stable isotope technique: of [U-13C]-palmitate (0.0026 mg kg-1 min-1, primed by a 0.085 mg kg-1 NaH13CO3 bolus) fat metabolism was measured at fed state and during 24 hours of fasting

  2. Change in carbohydrates metabolisms from fed to fasted state [ Time Frame: 24 hours ]
    Using indirect calorimetri and stable isotope technique: of [D2]-glucose (0.0728 mg kg-1 min-1, primed by a 3.203 mg kg-1 D2- glucose bolus) glucose metabolism was measured at fed state and during 24 hours of fasting


Secondary Outcome Measures :
  1. Change in insulin, glucagon, epinephrine and norepinephrine and the metabolites palmitate, free fatty acids (FFA), glycerol, glucose, pyruvate, β-hydroxybuturate, acetoacetate from fed to fasted state. [ Time Frame: 24 hours ]
    Hormones and metabolites were measured at fed state and during 24 hours of fasting

  2. Change in glucagon from fed to fasted state. [ Time Frame: 24 hours ]
    Glucagon was measured at fed state and during 24 hours of fasting

  3. Change in epinephrine from fed to fasted state. [ Time Frame: 24 hours ]
    Epinephrine was measured at fed state and during 24 hours of fasting

  4. Change in norepinephrine from fed to fasted state. [ Time Frame: 24 hours ]
    Norepinephrine was measured at fed state and during 24 hours of fasting

  5. Change in palmitate from fed to fasted state. [ Time Frame: 24 hours ]
    Palmitate was measured at fed state and during 24 hours of fasting

  6. Change in free fatty acids (FFA) from fed to fasted state. [ Time Frame: 24 hours ]
    FFA was measured at fed state and during 24 hours of fasting

  7. Change in glycerol from fed to fasted state. [ Time Frame: 24 hours ]
    Glycerol was measured at fed state and during 24 hours of fasting

  8. Change in glucose from fed to fasted state. [ Time Frame: 24 hours ]
    Glucose was measured at fed state and during 24 hours of fasting

  9. Change in pyruvate from fed to fasted state. [ Time Frame: 24 hours ]
    Pyruvate was measured at fed state and during 24 hours of fasting

  10. Change in β-hydroxybuturate from fed to fasted state. [ Time Frame: 24 hours ]
    β-hydroxybuturatewas measured at fed state and during 24 hours of fasting

  11. Change in acetoacetate from fed to fasted state. [ Time Frame: 24 hours ]
    Acetoacetate was measured at fed state and during 24 hours of fasting


Eligibility Criteria
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Ages Eligible for Study:   1 Year to 80 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Patients with low skeletal muscle mass

Exclusion Criteria:

  • Competing disorders interfering with interpretation of results
  • Medication that will interfere with results
  • Compliance problems
  • Participation in other clinical trials that will interfere with interpretation of results
  • Pregnancy or breastfeeding
Contacts and Locations

Locations
Layout table for location information
Denmark
Copenhagen Neuromuscular Center
Copenhagen, Denmark, 2200
Sponsors and Collaborators
Rigshospitalet, Denmark
Tracking Information
First Submitted Date  ICMJE May 21, 2019
First Posted Date  ICMJE May 31, 2019
Last Update Posted Date May 31, 2019
Actual Study Start Date  ICMJE May 29, 2017
Actual Primary Completion Date November 30, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 29, 2019)
  • Change in fat metabolisms from fed to fasted state [ Time Frame: 24 hours ]
    Using indirect calorimetri and stable isotope technique: of [U-13C]-palmitate (0.0026 mg kg-1 min-1, primed by a 0.085 mg kg-1 NaH13CO3 bolus) fat metabolism was measured at fed state and during 24 hours of fasting
  • Change in carbohydrates metabolisms from fed to fasted state [ Time Frame: 24 hours ]
    Using indirect calorimetri and stable isotope technique: of [D2]-glucose (0.0728 mg kg-1 min-1, primed by a 3.203 mg kg-1 D2- glucose bolus) glucose metabolism was measured at fed state and during 24 hours of fasting
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: May 29, 2019)
  • Change in insulin, glucagon, epinephrine and norepinephrine and the metabolites palmitate, free fatty acids (FFA), glycerol, glucose, pyruvate, β-hydroxybuturate, acetoacetate from fed to fasted state. [ Time Frame: 24 hours ]
    Hormones and metabolites were measured at fed state and during 24 hours of fasting
  • Change in glucagon from fed to fasted state. [ Time Frame: 24 hours ]
    Glucagon was measured at fed state and during 24 hours of fasting
  • Change in epinephrine from fed to fasted state. [ Time Frame: 24 hours ]
    Epinephrine was measured at fed state and during 24 hours of fasting
  • Change in norepinephrine from fed to fasted state. [ Time Frame: 24 hours ]
    Norepinephrine was measured at fed state and during 24 hours of fasting
  • Change in palmitate from fed to fasted state. [ Time Frame: 24 hours ]
    Palmitate was measured at fed state and during 24 hours of fasting
  • Change in free fatty acids (FFA) from fed to fasted state. [ Time Frame: 24 hours ]
    FFA was measured at fed state and during 24 hours of fasting
  • Change in glycerol from fed to fasted state. [ Time Frame: 24 hours ]
    Glycerol was measured at fed state and during 24 hours of fasting
  • Change in glucose from fed to fasted state. [ Time Frame: 24 hours ]
    Glucose was measured at fed state and during 24 hours of fasting
  • Change in pyruvate from fed to fasted state. [ Time Frame: 24 hours ]
    Pyruvate was measured at fed state and during 24 hours of fasting
  • Change in β-hydroxybuturate from fed to fasted state. [ Time Frame: 24 hours ]
    β-hydroxybuturatewas measured at fed state and during 24 hours of fasting
  • Change in acetoacetate from fed to fasted state. [ Time Frame: 24 hours ]
    Acetoacetate was measured at fed state and during 24 hours of fasting
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Fat and Glucose Metabolism in Fed and Fasted State in Patients With Low Skeletal Muscle Mass
Official Title  ICMJE Fedt og Sukkerstofskiftet Under Faste Hos Patienter Med Lav Muskelmasse.
Brief Summary In a study from 2003 the investigators showed that adult patients with very low skeletal muscle mass (spinal muscular atrophy (SMA) type II, Duchenne muscular dystrophy, congenital muscular dystrophy) are prone to develop hypoglycemia during prolonged fasting. Since then case reports have described the same phenomenon with hypoglycemia and metabolic crises in children with low skeletal muscle mass provoked by infection, fasting and surgery. Pathophysiological mechanisms of metabolism have never been investigated in adults or children with SMA II. Thus the investigators studied fat and glucose metabolism during prolonged fasting in patients with SMA II and LAMA 2 and compared results to those found in healthy controls.
Detailed Description

Design. This is a prospective case-control study investigating fat and glucose metabolism in patients with low muscle mass during prolonged fasting, comparing results to those found in healthy controls.

Setting. All children were admitted to the Department of Pediatrics and Adolescents medicine, Rigshospitalet, and all adult subjects were admitted to the Department of Neurology, Rigshospitalet at 4 pm for a 24-hour fasting period.

Protocol. The protocol consisted of two visits. A pre-experimental visit and a study visit.

Pre-experimental visit. Total muscle mass presented as lean body mass (LBM) was measured by DEXA scan. Furthermore, pre-experimental preparations included that all subjects were instructed to follow national nutritional recommendations with a healthy diet consisting of less than 30% fat, low fat protein, long chain carbohydrates and minimize sugar intake three days before the study.

Study visit. Patients were admitted to the hospital at 16:00 hours for IV catheter placement and a standardized evening meal at 17:00. Two venous catheters were inserted, one in the cubital vein (for stable-isotope infusion) and one in the distal cephalic vein (for blood sampling). A heating pad, covering the hand and distal forearm, ensured shunting of arterial blood to the veins in order to obtain arterialized blood. A primed, constant rate infusion of [U-13C]-palmitate (0.0026 mg kg-1 min-1, primed by a 0.085 mg kg-1 NaH13CO3 bolus) and [D2]-glucose (0.0728 mg kg-1 min-1, primed by a 3.203 mg kg-1 D2- glucose bolus) was delivered by a Gemini PC2 pump (IMED, San Diego, CA). Preparation of tracers and tracer calculations were performed as described.

Blood and air samples were collected just before start of infusion of the stable isotopes, and again after 2, 10, 14, 16, 18, 20, 22 and 24 hours of fasting (figure 1). Gas exchange measurements (indirect calorimetry) were performed with a metabolic cart (Cosmed Quark b2; Cosmed Srl., Milan, Italy). At the same time-points, expired air was collected in a 15 L Douglas bag (Hans Rudolph, Kansas City, MO, USA) and 10 mL samples were transferred to vacuum tubes (Vacutainer, BD, Franklin Lakes, NJ, USA) for 13CO2 analysis.

The blood glucose levels were monitored continuously at all blood sampling times and every third hour during the night in the patients. If the subjects developed symptoms of hypoglycaemia (fatigue, dizziness, nausea) the blood sugar was measured immediately. The fasting period lasted 24 hours or until signs of hypoglycemia as mentioned above or blood glucose below 3.0 mmol/L. Patients received an IV bolus of 10% glucose according to weight if signs of hypoglycemia occurred.

Analyses of blood samples and expired 13CO2. Venous blood was transferred to cooled tubes with EDTA (Ethylenediaminetetraacetic acid) (0.33M, 10μL mL-1) and spun at 4,000 rpm for 10 minutes. Plasma was distributed to Eppendorf tubes and immediately frozen on dry ice and stored at -80°C until analysis. Plasma insulin and glucagon analyses were performed at the Department of Clinical Biochemistry at Rigshospitalet, Copenhagen, Denmark (Cobas 8000, Roche, Rotkreuz Switzerland). Plasma free fatty acids and catecholamines were analyzed by spectrophotometry (Multiskan GO, Thermo Scientific, SkanIt™ Software, Thermo Fisher Scientific Inc., USA). Plasma palmitate, β-hydroxybuturate, acetoacetate, pyruvate, glycerol and amino acids as well as 13CO2-breath enrichment were analyzed by gas chromatography isotope ratio-mass spectrometry (Thermo Finnigan MAT GmbH, Bremen, Germany). Isotope tracer enrichments were determined using gas chromatography-mass spectrometry (Thermo Finnigan MAT GmbH, Bremen, Germany).

Glucose and lactate were analyzed on (ABL 700) immediately as the blood was drawn.

Shofield equation was used to calculate expected basal metabolic rate for the children: Males 10-17 years: (17.7 x weight+657+105) and females 10-17 years: (13,4 x weight+692+112) and the results were compared with the resting metabolic rate (RMR) measured by indirect calorimetric, as described above, at the end of the study, were patients had been resting and fasting for more than 8 hours.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE
  • Spinal Muscular Atrophy
  • Merosin Deficient Congenital Muscular Dystrophy
Intervention  ICMJE Other: Fasting
Fasting for 24 hours or until hypoglycemia (blood glucose < 3mmol/L) or symptoms of hypoglycemia
Study Arms  ICMJE Experimental: Fasting
Intervention: Other: Fasting
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 29, 2019)
13
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE November 30, 2017
Actual Primary Completion Date November 30, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients with low skeletal muscle mass

Exclusion Criteria:

  • Competing disorders interfering with interpretation of results
  • Medication that will interfere with results
  • Compliance problems
  • Participation in other clinical trials that will interfere with interpretation of results
  • Pregnancy or breastfeeding
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 80 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Denmark
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03970135
Other Study ID Numbers  ICMJE H-16049377
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Mette Cathrine Oerngreen, Rigshospitalet, Denmark
Study Sponsor  ICMJE Rigshospitalet, Denmark
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Rigshospitalet, Denmark
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP