Early Treatment of Amyotrophic Lateral Sclerosis (ALS) With Nutrition and Non-Invasive Positive Pressure Ventilation

Study Overview
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Brief Summary
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The purposes of the study are to determine the energy balance and evaluate the nutritional status of patients with ALS, and to investigate the use of NIPPV as respiratory support to treat patients with ALS.

Detailed Description
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Studies to date indicate that percutaneous endoscopic gastrostomy (PEG)-insertion of a feeding tube in the stomach-and non-invasive positive pressure ventilation (NIPPV)-mechanically assisted or generated breaths delivered through a tightly fitting nasal or facial mask-improve survival in amyotrophic lateral sclerosis (ALS), even when introduced late in the disease. Dr. Kasarskis and his research team believe early intervention with these treatments may improve patients outcome even further. However, many issues regarding the early use of these treatments prevent the design of a phase III clinical trial to test this hypothesis. Common to both NIPPV and nutrition is a lack of a reliable indicator of early respiratory or nutritional insufficiency. With respect to nutrition, reliable and cost effective methods are needed to determine a patient's energy (i.e. caloric) requirements at different stages of the illness to establish a basis for recommending PEG on the adequacy of energy intake. For NIPPV, factors that influence acceptance and tolerability of this therapy, and measurements of early respiratory dysfunction need to be identified. The purposes of this trial are to develop and validate strategies to improve tolerability of NIPPV, identify factors that influence acceptance of NIPPV, and evaluate measures of early respiratory failure, other than percentage of forced vital capacity (FVC). Researchers will also develop and validate methods to determine energy balance in and evaluate the nutritional status of patients with ALS that will be applicable to a multi-center phase III study of nutrition and NIPPV. The study will be conducted at 11 other sites across the country. Some study sites will focus on the nutritional aspects of the trial while the other sites will focus on NIPPV treatment. A total of 220 patients will be studied over 2 years. Enrollment will end on June 30, 2007. The last patient was followed clinically until June 30, 2008. The study remained open for sample analysis, data analysis, and assessment of vital status until the completion of funding on November 30, 2009.

Official Title
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Early Treatment of Amyotrophic Lateral Sclerosis With Nutrition and Non-Invasive Positive Pressure Ventilation

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Device: Early NIPPV
* Device: Standard NIPPV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to give informed consent. If women of childbearing age, must be non-lactating and surgically sterile or using an effective method of birth control (double-barrier or oral contraception) and have a negative pregnancy test. Minorities: All races and ethnic backgrounds. Disease inclusion: Clinically possible/definite/probable, or laboratory supported probable, sporadic or familial ALS according to the revised Escorial criteria. Onset of progressive weakness within 60 months prior to study. Willing to return for visits as scheduled and adhere to protocol requirements. FVC Criteria NIPPV Arm: Best-sitting FVC between 50% and 95% of predicted normal. Nutrition Arm: Best-sitting FVC >50% of predicted normal. Exclusion Criteria: Untreated or unstable hyper or hypothyroidism, untreated or unstable asthma, unstable angina, advanced liver or renal disease, advanced cancer, untreated diabetes or chronic obstructive pulmonary disease (COPD). Diagnosis of other motor neuron or other neurological disorder that mimics ALS. Diagnosis of other neurodegenerative disease (i.e., Parkinson's disease, Alzheimer's disease, etc.) Inflammatory bowel disease or malabsorption syndrome. Use of NIPPV, mechanical ventilation, or tracheostomy at the time of consent. Inability to adhere to study visit schedule or lack of reliable caretaker if participant requires one. Pregnant or lactating woman.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early NIPPV Intervention<br>Participants with >80% predicted forced vital capacity (FVC). | Device: Early NIPPV<br>* Early intervention with non-invasive positive pressure ventilation (NIPPV) at 80% forced vital capacity (FVC).<br>* Other names: BiPAP (Bilevel Positive Airway Pressure);|
| Active Comparator: Standard of Care NIPPV<br>Participants with 50-74% predicted forced vital capacity (FVC). | Device: Standard NIPPV<br>* Standard of care non-invasive positive pressure ventilation (NIPPV) at 50% forced vital capacity (FVC).<br>* Other names: BiPAP (Bilevel Positive Airway Pressure);|
| Active Comparator: Standard of Care NIPPV and Nutritional Monitoring<br>Participants with 50-95% forced vital capacity (FVC), and normal or impaired amyotrophic lateral sclerosis functional rating scale (ALSFRS) scores. Participants in this group will receive standard of care NIPPV therapy but will also undergo detailed analysis of nutritional status. | Device: Standard NIPPV<br>* Standard of care non-invasive positive pressure ventilation (NIPPV) at 50% forced vital capacity (FVC).<br>* Other names: BiPAP (Bilevel Positive Airway Pressure);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acceptance Rate of Early Non-invasive Positive Pressure Ventilation (NIPPV) Treatment. | Percentage of patients attempting to use NIPPV therapy within six weeks of initial offer. | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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amyotrophic lateral sclerosis, ALS, Lou Gehrig's disease, nutrition, NIPPV, non-invasive positive pressure ventilation, percutaneous endoscopic gastrostomy, PEG