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.