Clinical trial NCT00116558: Early Treatment of Amyotrophic Lateral Sclerosis (ALS) With Nutrition and Non-Invasive Positive Pressure Ventilation
Official title: Early Treatment of Amyotrophic Lateral Sclerosis With Nutrition and Non-Invasive Positive Pressure Ventilation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Amyotrophic Lateral Sclerosis
Keywords: amyotrophic lateral sclerosis
ALS
Lou Gehrig's disease
nutrition
NIPPV
non-invasive positive pressure ventilation
percutaneous endoscopic gastrostomy
PEG
Lead sponsor: University of Kentucky
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2005-06-30
Enrollment: 153
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

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.

Primary outcomes:
measure: Acceptance Rate of Early Non-invasive Positive Pressure Ventilation (NIPPV) Treatment.
timeFrame: 6 weeks
Secondary outcomes:
Other outcomes:
measure: Patient Survival With Early Versus Standard of Care NIPPV Treatment
timeFrame: one year
measure: Compliance With NIPPV Treatment
timeFrame: one month
measure: Total Daily Energy Expediture (TDEE) of ALS Patients
timeFrame: Duration of study (approximately 1 year)
measure: Tolerance of NIPPV Treatment
timeFrame: one month
Locations:
city: Denver
country: United States
facility: University of Colorado
state: Colorado
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: New York
country: United States
facility: Beth Israel
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Syracuse
country: United States
facility: SUNY
state: New York
city: Hershey
country: United States
facility: Pennsylvania State University
state: Pennsylvania
city: Philadelphia
country: United States
facility: Drexel University
state: Pennsylvania
city: San Antonio
country: United States
facility: University of Texas-San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Burlington
country: United States
facility: University of Vermont
state: Vermont
Study officials:
affiliation: University of Kentucky
name: Edward Kasarskis, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
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: 10.3109/17482968.2010.515225.