Amyotrophic Lateral Sclerosis
Conditions
Keywords
amyotrophic lateral sclerosis, ALS, Lou Gehrig's disease, nutrition, NIPPV, non-invasive positive pressure ventilation, percutaneous endoscopic gastrostomy, PEG
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.
Interventions
DEVICEEarly NIPPV
Early intervention with non-invasive positive pressure ventilation (NIPPV) at 80% forced vital capacity (FVC).
DEVICEStandard NIPPV
Standard of care non-invasive positive pressure ventilation (NIPPV) at 50% forced vital capacity (FVC).
Sponsors
National Institute of Neurological Disorders and Stroke (NINDS)
Edward Kasaraskis
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Acceptance Rate of Early Non-invasive Positive Pressure Ventilation (NIPPV) Treatment. | 6 weeks | Percentage of patients attempting to use NIPPV therapy within six weeks of initial offer. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Patient Survival With Early Versus Standard of Care NIPPV Treatment | one year | Duration of patient survival |
| Compliance With NIPPV Treatment | one month | Number of hours of NIPPV use per month |
| Total Daily Energy Expediture (TDEE) of ALS Patients | Duration of study (approximately 1 year) | Total daily energy expenditure (TDEE) with be measured using the dual labeled water (DLW) method |
| Tolerance of NIPPV Treatment | one month | Percent of patients achieving tolerance (\>4hr/night NIPPV after 2-3 week titration period) determined by actual usage data. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 80 |
| Standard of Care NIPPV Participants with 50-74% predicted forced vital capacity (FVC). | 26 |
| Early NIPPV Intervention Participants with \>80% predicted forced vital capacity (FVC). | 47 |
| Total | 153 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 11 | 5 | 3 |
| Overall Study | disease progression | 3 | 7 | 18 |
| Overall Study | Withdrawal by Subject | 17 | 3 | 12 |
Baseline characteristics
| Characteristic | Standard of Care NIPPV and Nutritional Monitoring | Standard of Care NIPPV | Early NIPPV Intervention | Total |
|---|---|---|---|---|
| Age, Continuous | 59.0 years STANDARD_DEVIATION 11.7 | 60.8 years STANDARD_DEVIATION 11.4 | 56.2 years STANDARD_DEVIATION 11.2 | 58.6 years STANDARD_DEVIATION 11.6 |
| Region of Enrollment United States | 80 participants | 26 participants | 47 participants | 153 participants |
| Sex: Female, Male Female | 28 Participants | 10 Participants | 17 Participants | 55 Participants |
| Sex: Female, Male Male | 52 Participants | 16 Participants | 30 Participants | 98 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 19 / 153 |
| other Total, other adverse events | 62 / 153 |
| serious Total, serious adverse events | 42 / 153 |
Outcome results
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.
Time frame: 6 weeks
Population: Data were not obtained from the Standard of Care NIPPV and Nutritional Monitoring arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard of Care NIPPV and Nutritional Monitoring | Acceptance Rate of Early Non-invasive Positive Pressure Ventilation (NIPPV) Treatment. | 0 Participants |
| Standard of Care NIPPV | Acceptance Rate of Early Non-invasive Positive Pressure Ventilation (NIPPV) Treatment. | 23 Participants |
| Early NIPPV Intervention | Acceptance Rate of Early Non-invasive Positive Pressure Ventilation (NIPPV) Treatment. | 35 Participants |
Other Pre-specified
Compliance With NIPPV Treatment
Number of hours of NIPPV use per month
Time frame: one month
Other Pre-specified
Patient Survival With Early Versus Standard of Care NIPPV Treatment
Duration of patient survival
Time frame: one year
Other Pre-specified
Tolerance of NIPPV Treatment
Percent of patients achieving tolerance (\>4hr/night NIPPV after 2-3 week titration period) determined by actual usage data.
Time frame: one month
Population: No data were collected for the Standard of Care NIIPPV and Nutritional Monitoring arm.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Standard of Care NIPPV and Nutritional Monitoring | Tolerance of NIPPV Treatment | 0 Participants |
| Standard of Care NIPPV | Tolerance of NIPPV Treatment | 11 Participants |
| Early NIPPV Intervention | Tolerance of NIPPV Treatment | 14 Participants |
Other Pre-specified
Total Daily Energy Expediture (TDEE) of ALS Patients
Total daily energy expenditure (TDEE) with be measured using the dual labeled water (DLW) method
Time frame: Duration of study (approximately 1 year)