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

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.

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