Quantitative Measurement of Nutritional Substrate Utilization in Patients With Amyotrophic Lateral Sclerosis (ALS)

This study has been terminated.
(Lack of funding and support staff.)
Sponsor:
Collaborator:
MDA/ALS Center of Hope
Information provided by (Responsible Party):
Drexel University ( Drexel University College of Medicine )
ClinicalTrials.gov Identifier:
NCT00714220
First received: July 10, 2008
Last updated: May 1, 2014
Last verified: March 2013
  Purpose

The work of Nau et. al (Nau KL, Bromberg MB, Forshew DA, Katcha Vl. Individuals with amyotrophic lateral sclerosis are in caloric balance despite losses in mass. J Neurol Sci 1995;129 :47-49) showed that patients in the early stages of ALS initially increase their body fat. Another study showed that advanced ALS patients on mechanical ventilation were actually hypometabolic, supporting a hypothesis that ALS patients' daily oral intakes of calories fail to match their energy requirements, thus exacerbating their condition. This current study investigates and compares substrate utilization using a metabolic cart in controls and in ALS patients who are on and off ventilatory support to examine differences in substrate utilization between the two groups of ALS patients and the controls. (Substrate utilization is essentially the percentage of fats, carbohydrates, and protein utilized by the body.) The study will increase our understanding of the nutritional needs of ALS patients and improve our ability to provide the best possible nutrition in progressive illness.


Condition
Amyotrophic Lateral Sclerosis
Neurodegenerative Diseases

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Cross-Sectional
Official Title: Quantitative Measurement of Nutritional Substrate Utilization in Patients With ALS

Resource links provided by NLM:


Further study details as provided by Drexel University:

Primary Outcome Measures:
  • Indirect Calorimetry [ Time Frame: 20 minute session ] [ Designated as safety issue: No ]
    Indirect calorimetry will be used to determine how many calories you are burning and how much of your total calories burned are fats.


Enrollment: 107
Study Start Date: November 2006
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
ALS
Subjects having either definite or probable ALS by El Escorial Criteria.
Neurological Control
Subjects having been diagnosed with a non-ALS neurological condition
Healthy Control
Subjects in good health without any neurological conditions

Detailed Description:

Study groups will include ALS patients with and without respiratory failure as judged by their FVC and use of either noninvasive or invasive ventilation along with normal controls. For all patients, nutritional status will be assessed by measurement of weight, and determination of Urinary Urea Nitrogen (via 24hr urinary sample), albumin and pre-albumin levels and questions regarding recent weight changes. In addition, for ALS patients, clinical data regarding the age of the patient, duration of disease, site of onset along with ALS-FRS (Amyotrophic Lateral Sclerosis Functional Rating Scale) and Pulmonary function testing will be collected. If these data are already available from chart as they are commonly performed during routine care, the data will be obtained from the patients chart.

5cc blood will be obtained for measurement of Serum albumin, pre-albumin and TNF-α. Antigenic TNF-α, bioactive TNF-α and receptors serum sTNF-RI and TNF-RII will be measured using the standard ELISA kits and cytolytic assays.

Respiratory Quotients (RQs) will be measured using a metabolic cart in both controls and ALS patients. First, the patient's VCO2 and VO2 will be measured - as the patient breaths into a mask connected to the machine.- RQ will be calculated using Lavoisier and Laplace's equation: RQ = VCO2/VO2.

This, however, is not an accurate representation because it considers only fats and carbohydrates as the sources for these gases. A corrected Non-Protein RQ (NPRQ) RQ will be calculated using a 24 hour urine sample and measuring the Urinary Urea Nitrogen (24hr UUN). This tells us the amount of protein oxidized per 24 hours. Then, applying the principle that one gram of urinary nitrogen represents the combustion of an amount of protein that requires 5.925L of oxygen and produces 4.75L of carbon dioxide, the amount of oxygen and carbon dioxide associated with protein metabolism will be calculated. This calculated VO2 and VCO2 will then be subtracted from the totals measured using the metabolic cart and the corrected Non-Protein RQ will be calculated.

The corrected respiratory quotient will then be used to calculate the amount of nutritional substrate utilization in the patient population using Table 7.2. Non-Protein Respiratory Quotient And The Relative Quantity Of Carbohydrate And Fat Oxidized And Energy Per Liter Of Oxygen (Appendix-I).v The amount (grams) of carbohydrate and fats utilized per each NPRQ will be recorded.

The protein catabolic rate (PCR) will also be calculated using the equation :

PCR=[24hr UUN(g) + 4] x 6.25 (g/day). The clinical information along with test results will be collected in a spreadsheet in which patients and controls are de-identified. This spreadsheet will be used for the analysis.

Primary endpoints are the analysis of nutritional substrate utilization with and without respiratory compromise. Secondary endpoints include the correlation of in the composition of substrate utilization between patients who use a ventilator and those who do not, those patients with and without a PEG Tube in each group, and correlation of substrate use with the stage of illness as judged by the ALSFRS score, weight changes and duration of disease.

This is a one time testing procedure, and the patient will not be asked to return back for another visit.

  Eligibility

Ages Eligible for Study:   20 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

ALS clinic patients at MDA/ALS Center of Hope.

Criteria

Inclusion Criteria:

  • Diagnosis of definite or possible ALS by the El Escorial Criteria
  • No previously known gastrointestinal problems

Exclusion Criteria:

  • Patients or controls who have evidence of previous gastrointestinal disease
  • Patients unable to give informed consent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00714220

Locations
United States, Pennsylvania
MDA/ALS Center of Hope
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Drexel University College of Medicine
MDA/ALS Center of Hope
  More Information

No publications provided

Responsible Party: Drexel University ( Drexel University College of Medicine )
ClinicalTrials.gov Identifier: NCT00714220     History of Changes
Other Study ID Numbers: Internal-16684
Study First Received: July 10, 2008
Last Updated: May 1, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Drexel University:
Amyotrophic Lateral Sclerosis
Gastric Motility
Autonomic Nervous System
Neurodegenerative Diseases
Movement Disorders
Substrate Utilization

Additional relevant MeSH terms:
Amyotrophic Lateral Sclerosis
Sclerosis
Motor Neuron Disease
Neurodegenerative Diseases
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
TDP-43 Proteinopathies
Neuromuscular Diseases
Proteostasis Deficiencies
Metabolic Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on August 27, 2014