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

Amyotrophic Lateral Sclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00116558
• Other study ID #: R01NS045087
• Secondary ID: R01NS045087
• Status: Completed
• Phase: N/A
• Start date: August 1, 2004
• Est. completion date: January 2012

Study information

• Verified date: July 2019
• Source: University of Kentucky
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 153
• Est. completion date: January 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Device:
• Early NIPPV
Early intervention with non-invasive positive pressure ventilation (NIPPV) at 80% forced vital capacity (FVC).
• Standard NIPPV
Standard of care non-invasive positive pressure ventilation (NIPPV) at 50% forced vital capacity (FVC).

Locations

Country	Name	City	State
United States	University of Vermont	Burlington	Vermont
United States	University of Colorado	Denver	Colorado
United States	Henry Ford Hospital	Detroit	Michigan
United States	Pennsylvania State University	Hershey	Pennsylvania
United States	University of Kentucky	Lexington	Kentucky
United States	University of Miami	Miami	Florida
United States	Beth Israel	New York	New York
United States	Columbia University	New York	New York
United States	Drexel University	Philadelphia	Pennsylvania
United States	University of Utah	Salt Lake City	Utah
United States	University of Texas-San Antonio	San Antonio	Texas
United States	SUNY	Syracuse	New York

Sponsors (2)

Lead Sponsor	Collaborator
Edward Kasaraskis	National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View Citation

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: 10.3109/17482 — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Patient Survival With Early Versus Standard of Care NIPPV Treatment	Duration of patient survival	one year
Other	Compliance With NIPPV Treatment	Number of hours of NIPPV use per month	one month
Other	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)
Other	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
Primary	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