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

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

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.

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Device: Early NIPPV; Device: Standard NIPPV

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.

• Study Type: Interventional
• Enrollment (Actual): 153
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80262
      • University of Colorado
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • New York
    • New York, New York, United States, 10032
      • Columbia University
    • New York, New York, United States, 10003
      • Beth Israel
    • Syracuse, New York, United States, 13210
      • SUNY
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Pennsylvania State University
    • Philadelphia, Pennsylvania, United States, 19103
      • Drexel University
  • Texas
    • San Antonio, Texas, United States, 78229
      • University of Texas-San Antonio
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah
  • Vermont
    • Burlington, Vermont, United States, 54505
      • University of Vermont

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / 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 Names: 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 Names: 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 Names: BiPAP (Bilevel Positive Airway Pressure)

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Survival With Early Versus Standard of Care NIPPV Treatment	Duration of patient survival	one year
Compliance With NIPPV Treatment	Number of hours of NIPPV use per month	one month
Total Daily Energy Expediture (TDEE) of ALS Patients	Total daily energy expenditure (TDEE) with be measured using the dual labeled water (DLW) method	Duration of study (approximately 1 year)
Tolerance of NIPPV Treatment	Percent of patients achieving tolerance (>4hr/night NIPPV after 2-3 week titration period) determined by actual usage data.	one month

Collaborators and Investigators

• Sponsor: Edward Kasaraskis
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Edward Kasarskis, MD, PhD, University of Kentucky

Publications and helpful links

General Publications

• Kasarskis EJ, Mendiondo MS, Matthews DE, Mitsumoto H, Tandan R, Simmons Z, Bromberg MB, Kryscio RJ; ALS Nutrition/NIPPV Study Group. Estimating daily energy expenditure in individuals with amyotrophic lateral sclerosis. Am J Clin Nutr. 2014 Apr;99(4):792-803. doi: 10.3945/ajcn.113.069997. Epub 2014 Feb 12.
• Scagnelli CN, Howard DB, Bromberg MB, Kasarskis EJ, Matthews DE, Mitsumoto HM, Simmons Z, Tandan R; ALS Nutrition-NIPPV Study Group. Hydration measured by doubly labeled water in ALS and its effects on survival. Amyotroph Lateral Scler Frontotemporal Degener. 2018 May;19(3-4):220-231. doi: 10.1080/21678421.2017.1413117. Epub 2017 Dec 15.
• Kasarskis EJ, Mendiondo MS, Wells S, Malguizo MS, Thompson M, Healey M, Kryscio RJ; ALS Nutrition/NIPPV Study Group. The ALS Nutrition/NIPPV Study: design, feasibility, and initial results. Amyotroph Lateral Scler. 2011 Jan;12(1):17-25. doi: 10.3109/17482968.2010.515225.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2004
• Primary Completion (Actual): January 1, 2012
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: June 29, 2005
• First Submitted That Met QC Criteria: June 29, 2005
• First Posted (Estimate): June 30, 2005

Study Record Updates

• Last Update Posted (Actual): July 31, 2019
• Last Update Submitted That Met QC Criteria: July 11, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: ALS; nutrition; amyotrophic lateral sclerosis; Lou Gehrig's disease; PEG; NIPPV; non-invasive positive pressure ventilation; percutaneous endoscopic gastrostomy
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: R01NS045087 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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