Study of Standard Noninvasive Positive Pressure Ventilation (NIPPV) and Low Expiratory Pressure NIPPV in ALS Patients

• Sponsor: Kirsten Gruis (Other)
• Overall Status: Completed
• CT.gov ID: NCT01154283
• Collaborator: ALS Association (Other)
• Enrollment: 28
• Location: 1
• Arms: 2
• Duration (Months): 45
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The purpose of the study is to test whether noninvasive positive pressure ventilation (NIPPV) without expiratory positive airway pressure (EPAP) (inspiratory positive airway pressure (IPAP)-only) will result in an increase in patient usage of NIPPV compared with standard, Bi-level NIPPV. Secondarily, the investigators will assess measures of dyspnea, quality of life, patient satisfaction, and side effects.

Condition or Disease	Intervention/Treatment	Phase
Amyotrophic Lateral Sclerosis	Device: Viasys® Healthcare, Pulmonetic Systems, lap-top ventilator (LTV machine)	N/A

Detailed Description

Subjects will be randomized on a 1:1 basis to one of two groups differing in the sequence of NIPPV settings ((a) standard, Bi-level NIPPV followed by IPAP-only NIPPV or (b) IPAP-only NIPPV followed by standard, Bi-level, NIPPV). Subjects will then spend 6 weeks using the first NIPPV set-up before crossing over to the other NIPPV treatment for 6 weeks. At the beginning of the study, subjects will undergo approximately two hours of training and education by a respiratory therapist regarding proper use of the Viasys® Healthcare, Pulmonetic Systems, lap-top ventilators (LTV machine). They will be fitted with the appropriate NIPPV set-up. The patients will use the same mask interface with the study NIPPV machine that they were using with their NIPPV (bi-level positive airway pressure (BiPAP)) machine prior to study entry.

The patients will have two additional study visits after the consent/training session: one at the end of 6 weeks, after the first NIPPV treatment period (prior to crossing over to the second NIPPV treatment), and the second at the end of 12 weeks, after the second NIPPV treatment period.

NIPPV usage will be recorded as hours of use as measured objectively by the NIPPV machine hour meter. When the patient returns for his/her first study visit at the end of week six, the NIPPV machine hour meter will be recorded by the study investigator. By subtracting the hours recorded at the beginning of week two from the hours recorded at the end of week six, the NIPPV hours of usage for weeks two, three, four, five and six will be obtained. This same procedure will be repeated to record NIPPV hours of usage for the beginning of week eight and the end of week twelve to measure the hours of usage with the second NIPPV set-up for weeks eight, nine, ten, eleven and twelve. This allows study subjects one week to adjust to the new pressure settings of each treatment arm.

Dyspnea as measured by the transition dyspnea index (TDI), and quality of life as measured by the EuroQol Visual analogue scale(VAS) will be re-administered at both 6 and 12 week study visits by study personnel. Lastly, patient preference of NIPPV treatment will be subjectively assessed at the 12 week study visit on a Likert scale (definitely first treatment, probably first treatment, no preference, probably second treatment, definitely second treatment).

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: A Randomized Crossover Study of Standard, Noninvasive Positive Pressure Ventilation (NIPPV) and Low Expiratory Pressure NIPPV in Amyotrophic Lateral Sclerosis (ALS) Patients
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: Oct 1, 2011
• Actual Study Completion Date: Oct 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Bi-level, standard, NIPPV Standard NIPPV with both an inspiratory and expiratory positive airway pressure.	Device: Viasys® Healthcare, Pulmonetic Systems, lap-top ventilator (LTV machine); Noninvasive positive airway pressure ventilation
Experimental: IPAP-only, NIPPV NIPPV with only inspiratory positive airway pressure, no expiratory positive airway pressure	Device: Viasys® Healthcare, Pulmonetic Systems, lap-top ventilator (LTV machine); Noninvasive positive airway pressure ventilation

Outcome Measures

Primary Outcome Measures

1. Hours of NIPPV Usage [Assessed at 6 weeks (first intervention) and 12 weeks (second intervention)]

   Patients experienced the first intervention period during weeks 1-6 and the second intervention period during weeks 7-12. Patients were given one week to learn how to use the NIPPV equipment at the beginning of each intervention period. Therefore, only the total NIPPV hours used during the last 5 weeks of each intervention period were collected and divided by the number of weeks to obtain the average, weekly hours of NIPPV usage assessed at 6 weeks (first intervention) and 12 weeks (second intervention) for each patient.

Secondary Outcome Measures

1. Patient Preference (Likert Scale) "Definitely IPAP-only" "Probably IPAP-only" "Uncertain" "Probably Bi-level" "Definitely Bi-level" [Assessed at 6 weeks (first intervention) and 12 weeks (second intervention)]

   Patient Preference of NIPPV mode: definitely IPAP-only probably IPAP-only uncertain probably Bi-level definitely Bi-level Number of patients who chose definitely or probably are reported.

2. Transitional Dyspnea Index [Assessed at 6 weeks (first intervention) and 12 weeks (second intervention)]

   Transitional Dyspnea Index scores patient reported changes in difficulty breathing during each intervention period from -3 (major deterioration) to +3 (major improvement) in three categories: functional impairment, magnitude of task, and magnitude of effort. The total TDI score ranges from -9 to +9.

3. EuroQol Visual Analogue Scale(VAS) [Assessed at 6 weeks (first intervention) and 12 weeks (second intervention)]

   Quality of life assessed with visual analogue scale. Where the patient is asked to place a mark on a piece of paper with a vertical, scale from 100 at the top to 0 at the bottom of the scale. Where the patient is informed that 100 represents his or her best imaginable health state and 0 is his or her worst imaginable health state.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Age greater than 18 years

2. Definite or probable ALS by El Escorial criteria

3. Maximal inspiratory force < 60 cm/H2O or FVC <50% predicted (American College of Chest Physicians' criteria for initiating NIPPV)

4. Patients must have used NIPPV (typically administered as BiPAP) for at least 2 months

5. Currently using NIPPV ≥5 days a week with an EPAP = 4 cm H2O.

Exclusion Criteria:

1. Any medical condition that will interfere with participation

2. Inability to consent for him/herself

3. Known obstructive sleep apnea or obstructive pulmonary disease.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Michigan	Ann Arbor	Michigan	United States	48109

Sponsors and Collaborators

• Kirsten Gruis
• ALS Association

Investigators

• Principal Investigator: Kirsten Gruis, MD, University of Michigan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Kirsten Gruis, Associate Professor, University of Michigan
• ClinicalTrials.gov Identifier: NCT01154283
• Other Study ID Numbers: ALSA-9611
• First Posted: Jun 30, 2010
• Last Update Posted: Jan 2, 2017
• Last Verified: Nov 1, 2016

• Additional relevant MeSH terms: Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis

Study Results

Participant Flow

Arm/Group Title	Bi-level, Standard, NIPPV Then IPAP-only NIPPV	IPAP-only, NIPPV Then Bi-level, Standard NIPPV
Arm/Group Description	Standard NIPPV with both an inspiratory and expiratory positive airway pressure then NIPPV with only inspiratory positive airway pressure (IPAP-only), no expiratory positive airway pressure Viasys® Healthcare, Pulmonetic Systems, lap-top ventilator (LTV machine): Noninvasive positive airway pressure ventilation (NIPPV)	NIPPV with only inspiratory positive airway pressure (IPAP-only), no expiratory positive airway pressure then Standard NIPPV with both an inspiratory and expiratory positive airway pressure Viasys® Healthcare, Pulmonetic Systems, lap-top ventilator (LTV machine): Noninvasive positive airway pressure ventilation (NIPPV)
Period Title: 0-6 Weeks
STARTED	14	14
COMPLETED	7	11
NOT COMPLETED	7	3
Period Title: 0-6 Weeks
STARTED	7	11
COMPLETED	6	10
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Bi-level, Standard, NIPPV Then IPAP-only NIPPV	IPAP-only, NIPPV Then Bi-level, Standard NIPPV	Total
Arm/Group Description	Standard NIPPV with both an inspiratory and expiratory positive airway pressure then NIPPV with only inspiratory positive airway pressure (IPAP-only), no expiratory positive airway pressure Viasys® Healthcare, Pulmonetic Systems, lap-top ventilator (LTV machine): Noninvasive positive airway pressure ventilation (NIPPV)	NIPPV with only inspiratory positive airway pressure (IPAP-only), no expiratory positive airway pressure then Standard NIPPV with both an inspiratory and expiratory positive airway pressure Viasys® Healthcare, Pulmonetic Systems, lap-top ventilator (LTV machine): Noninvasive positive airway pressure ventilation (NIPPV)	Total of all reporting groups
Overall Participants	14	14	28
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	62	59	60
Gender (Count of Participants)
Female	6 42.9%	7 50%	13 46.4%
Male	8 57.1%	7 50%	15 53.6%

Outcome Measures

1. Primary Outcome

Title	Hours of NIPPV Usage
Description	Patients experienced the first intervention period during weeks 1-6 and the second intervention period during weeks 7-12. Patients were given one week to learn how to use the NIPPV equipment at the beginning of each intervention period. Therefore, only the total NIPPV hours used during the last 5 weeks of each intervention period were collected and divided by the number of weeks to obtain the average, weekly hours of NIPPV usage assessed at 6 weeks (first intervention) and 12 weeks (second intervention) for each patient.
Time Frame	Assessed at 6 weeks (first intervention) and 12 weeks (second intervention)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bi-level, Standard, NIPPV	IPAP-only, NIPPV
Arm/Group Description	Standard NIPPV with both an inspiratory and expiratory positive airway pressure. Viasys® Healthcare, Pulmonetic Systems, lap-top ventilator (LTV machine): Noninvasive positive airway pressure ventilation	NIPPV with only inspiratory positive airway pressure, no expiratory positive airway pressure Viasys® Healthcare, Pulmonetic Systems, lap-top ventilator (LTV machine): Noninvasive positive airway pressure ventilation
Measure Participants	17	17
Mean (Full Range) [hours]	49.94	45.75

2. Secondary Outcome

Title	Patient Preference (Likert Scale) "Definitely IPAP-only" "Probably IPAP-only" "Uncertain" "Probably Bi-level" "Definitely Bi-level"
Description	Patient Preference of NIPPV mode: definitely IPAP-only probably IPAP-only uncertain probably Bi-level definitely Bi-level Number of patients who chose definitely or probably are reported.
Time Frame	Assessed at 6 weeks (first intervention) and 12 weeks (second intervention)

Outcome Measure Data

Analysis Population Description

One patient died before completion of 12 weeks (second intervention) and could not have patient preference assessed.

Arm/Group Title	Bi-level, Standard, NIPPV	IPAP-only, NIPPV
Arm/Group Description	Standard NIPPV with both an inspiratory and expiratory positive airway pressure. Viasys® Healthcare, Pulmonetic Systems, lap-top ventilator (LTV machine): Noninvasive positive airway pressure ventilation	NIPPV with only inspiratory positive airway pressure, no expiratory positive airway pressure Viasys® Healthcare, Pulmonetic Systems, lap-top ventilator (LTV machine): Noninvasive positive airway pressure ventilation
Measure Participants	16	16
Number [participants]	2 14.3%	12 85.7%

3. Secondary Outcome

Title	Transitional Dyspnea Index
Description	Transitional Dyspnea Index scores patient reported changes in difficulty breathing during each intervention period from -3 (major deterioration) to +3 (major improvement) in three categories: functional impairment, magnitude of task, and magnitude of effort. The total TDI score ranges from -9 to +9.
Time Frame	Assessed at 6 weeks (first intervention) and 12 weeks (second intervention)

Outcome Measure Data

Analysis Population Description

One patient died and unable to report dyspnea at end of 12 weeks. Two additional patients completed 12 weeks study but did not complete dyspnea assessments.

Arm/Group Title	Bi-level, Standard, NIPPV	IPAP-only, NIPPV
Arm/Group Description	Standard NIPPV with both an inspiratory and expiratory positive airway pressure. Viasys® Healthcare, Pulmonetic Systems, lap-top ventilator (LTV machine): Noninvasive positive airway pressure ventilation	NIPPV with only inspiratory positive airway pressure, no expiratory positive airway pressure Viasys® Healthcare, Pulmonetic Systems, lap-top ventilator (LTV machine): Noninvasive positive airway pressure ventilation
Measure Participants	14	14
Mean (Standard Deviation) [units on a scale]	-3.14 (2.98)	-1.21 (2.72)

4. Secondary Outcome

Title	EuroQol Visual Analogue Scale(VAS)
Description	Quality of life assessed with visual analogue scale. Where the patient is asked to place a mark on a piece of paper with a vertical, scale from 100 at the top to 0 at the bottom of the scale. Where the patient is informed that 100 represents his or her best imaginable health state and 0 is his or her worst imaginable health state.
Time Frame	Assessed at 6 weeks (first intervention) and 12 weeks (second intervention)

Outcome Measure Data

Analysis Population Description

One patient died and unable to report quality of life at end of 12 weeks. Two additional patients completed 12 weeks study but did not complete quality of life assessments.

Arm/Group Title	Bi-level, Standard, NIPPV	IPAP-only, NIPPV
Arm/Group Description	Standard NIPPV with both an inspiratory and expiratory positive airway pressure. Viasys® Healthcare, Pulmonetic Systems, lap-top ventilator (LTV machine): Noninvasive positive airway pressure ventilation	NIPPV with only inspiratory positive airway pressure, no expiratory positive airway pressure Viasys® Healthcare, Pulmonetic Systems, lap-top ventilator (LTV machine): Noninvasive positive airway pressure ventilation
Measure Participants	14	14
Mean (Standard Deviation) [units on a scale]	52.86 (25.32)	62.79 (17.28)

Adverse Events

Time Frame	Collected during study intervention time frame of 12 weeks.
Arm/Group Title	Bi-level, Standard, NIPPV		IPAP-only, NIPPV
Arm/Group Description	Standard NIPPV with both an inspiratory and expiratory positive airway pressure. Viasys® Healthcare, Pulmonetic Systems, lap-top ventilator (LTV machine): Noninvasive positive airway pressure ventilation (NIPPV)		NIPPV with only inspiratory positive airway pressure (IPAP-only), no expiratory positive airway pressure. Viasys® Healthcare, Pulmonetic Systems, lap-top ventilator (LTV machine): Noninvasive positive airway pressure ventilation (NIPPV)
All Cause Mortality
	Bi-level, Standard, NIPPV		IPAP-only, NIPPV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Bi-level, Standard, NIPPV		IPAP-only, NIPPV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/28 (7.1%)		2/28 (7.1%)
Gastrointestinal disorders
Dysphagia	0/28 (0%)		1/28 (3.6%)
Gastrointestinal motility and defaecation conditions	0/28 (0%)		1/28 (3.6%)
Infections and infestations
Lower Respiratory Tract Infection	1/28 (3.6%)		0/28 (0%)
Urinary Tract Infection	0/28 (0%)		1/28 (3.6%)
Respiratory, thoracic and mediastinal disorders
Bronchial Disorder	0/28 (0%)		1/28 (3.6%)
Pulmonary Embolism	1/28 (3.6%)		0/28 (0%)
Respiratory failure	1/28 (3.6%)		0/28 (0%)
Other (Not Including Serious) Adverse Events
	Bi-level, Standard, NIPPV		IPAP-only, NIPPV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/28 (25%)		5/28 (17.9%)
Gastrointestinal disorders
Dysphagia	3/28 (10.7%)		0/28 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	3/28 (10.7%)		3/28 (10.7%)
Cough Decreased	1/28 (3.6%)		2/28 (7.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.