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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00116558
Recruitment Status : Completed
First Posted : June 30, 2005
Results First Posted : July 31, 2019
Last Update Posted : July 31, 2019
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Edward Kasaraskis, University of Kentucky

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Amyotrophic Lateral Sclerosis Device: Early NIPPV Device: Standard NIPPV Not Applicable

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 153 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: Early Treatment of Amyotrophic Lateral Sclerosis With Nutrition and Non-Invasive Positive Pressure Ventilation
Actual Study Start Date : August 1, 2004
Actual Primary Completion Date : January 2012
Actual Study Completion Date : January 2012

Arm Intervention/treatment
Experimental: Early NIPPV Intervention
Participants with >80% predicted forced vital capacity (FVC).
Device: Early NIPPV
Early intervention with non-invasive positive pressure ventilation (NIPPV) at 80% forced vital capacity (FVC).
Other Name: BiPAP (Bilevel Positive Airway Pressure)

Active Comparator: Standard of Care NIPPV
Participants with 50-74% predicted forced vital capacity (FVC).
Device: Standard NIPPV
Standard of care non-invasive positive pressure ventilation (NIPPV) at 50% forced vital capacity (FVC).
Other Name: BiPAP (Bilevel Positive Airway Pressure)

Active Comparator: Standard of Care NIPPV and Nutritional Monitoring
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
Standard of care non-invasive positive pressure ventilation (NIPPV) at 50% forced vital capacity (FVC).
Other Name: BiPAP (Bilevel Positive Airway Pressure)

Primary Outcome Measures :
  1. Acceptance Rate of Early Non-invasive Positive Pressure Ventilation (NIPPV) Treatment. [ Time Frame: 6 weeks ]
    Percentage of patients attempting to use NIPPV therapy within six weeks of initial offer.

Other Outcome Measures:
  1. Patient Survival With Early Versus Standard of Care NIPPV Treatment [ Time Frame: one year ]
    Duration of patient survival

  2. Compliance With NIPPV Treatment [ Time Frame: one month ]
    Number of hours of NIPPV use per month

  3. Total Daily Energy Expediture (TDEE) of ALS Patients [ Time Frame: Duration of study (approximately 1 year) ]
    Total daily energy expenditure (TDEE) with be measured using the dual labeled water (DLW) method

  4. Tolerance of NIPPV Treatment [ Time Frame: one month ]
    Percent of patients achieving tolerance (>4hr/night NIPPV after 2-3 week titration period) determined by actual usage data.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00116558

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United States, Colorado
University of Colorado
Denver, Colorado, United States, 80262
United States, Florida
University of Miami
Miami, Florida, United States, 33136
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536
United States, Michigan
Henry Ford Hospital
Detroit, Michigan, United States, 48202
United States, New York
Beth Israel
New York, New York, United States, 10003
Columbia University
New York, New York, United States, 10032
Syracuse, New York, United States, 13210
United States, Pennsylvania
Pennsylvania State University
Hershey, Pennsylvania, United States, 17033
Drexel University
Philadelphia, Pennsylvania, United States, 19103
United States, Texas
University of Texas-San Antonio
San Antonio, Texas, United States, 78229
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
United States, Vermont
University of Vermont
Burlington, Vermont, United States, 54505
Sponsors and Collaborators
Edward Kasaraskis
National Institute of Neurological Disorders and Stroke (NINDS)
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Principal Investigator: Edward Kasarskis, MD, PhD University of Kentucky

Publications of Results:
Other Publications:
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Responsible Party: Edward Kasaraskis, Principal Investigator, University of Kentucky Identifier: NCT00116558    
Other Study ID Numbers: R01NS045087 ( U.S. NIH Grant/Contract )
R01NS045087 ( U.S. NIH Grant/Contract )
First Posted: June 30, 2005    Key Record Dates
Results First Posted: July 31, 2019
Last Update Posted: July 31, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Edward Kasaraskis, University of Kentucky:
amyotrophic lateral sclerosis
Lou Gehrig's disease
non-invasive positive pressure ventilation
percutaneous endoscopic gastrostomy
Additional relevant MeSH terms:
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Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases