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

NCT ID: NCT00116558

Last Updated: 2019-07-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 153 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-08-01
• Study Completion Date: 2012-01-31

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.

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.

Conditions

Amyotrophic Lateral Sclerosis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Early NIPPV Intervention

Participants with \>80% predicted forced vital capacity (FVC).

Group Type: EXPERIMENTAL

Early NIPPV

Intervention Type: DEVICE

Early intervention with non-invasive positive pressure ventilation (NIPPV) at 80% forced vital capacity (FVC).

Standard of Care NIPPV

Participants with 50-74% predicted forced vital capacity (FVC).

Group Type: ACTIVE_COMPARATOR

Standard NIPPV

Intervention Type: DEVICE

Standard of care non-invasive positive pressure ventilation (NIPPV) at 50% forced vital capacity (FVC).

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.

Group Type: ACTIVE_COMPARATOR

Standard NIPPV

Intervention Type: DEVICE

Standard of care non-invasive positive pressure ventilation (NIPPV) at 50% forced vital capacity (FVC).

Interventions

Early NIPPV

Early intervention with non-invasive positive pressure ventilation (NIPPV) at 80% forced vital capacity (FVC).

Intervention Type: DEVICE

Standard NIPPV

Standard of care non-invasive positive pressure ventilation (NIPPV) at 50% forced vital capacity (FVC).

Intervention Type: DEVICE

Other Intervention Names

BiPAP (Bilevel Positive Airway Pressure); BiPAP (Bilevel Positive Airway Pressure)

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

Edward Kasaraskis

OTHER

Sponsor Role: lead

Responsible Party

Edward Kasaraskis

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Edward Kasarskis, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Kentucky

Locations

University of Colorado

Denver, Colorado, United States

University of Miami

Miami, Florida, United States

University of Kentucky

Lexington, Kentucky, United States

Henry Ford Hospital

Detroit, Michigan, United States

Beth Israel

New York, New York, United States

Columbia University

New York, New York, United States

SUNY

Syracuse, New York, United States

Pennsylvania State University

Hershey, Pennsylvania, United States

Drexel University

Philadelphia, Pennsylvania, United States

University of Texas-San Antonio

San Antonio, Texas, United States

University of Utah

Salt Lake City, Utah, United States

University of Vermont

Burlington, Vermont, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 24522445 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29243507 (View on PubMed)

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.

Reference Type: RESULT

PMID: 21271789 (View on PubMed)

Other Identifiers

R01NS045087

Identifier Type: NIH

Identifier Source: secondary_id

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R01NS045087

Identifier Type: NIH

Identifier Source: org_study_id

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