Characterization of Placebo Responses in Stable Asthma

• Sponsor: Brigham and Women's Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01143688
• Collaborator: National Center for Complementary and Integrative Health (NCCIH) (NIH)
• Enrollment: 39
• Location: 1
• Arms: 3
• Duration (Months): 48
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The investigators hypothesize that different placebos will have different effects on subjective and objective asthma outcomes compared with actual therapy and natural history. .

Subjects with asthma are randomly treated with placebo inhaler, placebo acupuncture, albuterol inhaler, or "no treatment" in random order, on three different occasions each. At each of the 12 visits, spirometry is performed repeatedly over 2 hours. Maximum FEV1 achieved and an 11-point, self-reported scale of improvement are examined.

Condition or Disease	Intervention/Treatment	Phase
Asthma Placebo Effects	Drug: albuterol; Drug: placebo inhaler; Procedure: placebo acupuncture	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 39 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Characterization of Placebo Responses in Stable Asthma
• Study Start Date: Jan 1, 2005
• Actual Primary Completion Date: Jan 1, 2009
• Actual Study Completion Date: Jan 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: albuterol inhaler albuterol	Drug: albuterol
Placebo Comparator: placebo inhaler placebo	Drug: placebo inhaler
Placebo Comparator: placebo acupuncture placebo	Procedure: placebo acupuncture

Outcome Measures

Primary Outcome Measures

1. Change in FEV1 [FEV1 was assessed every 20 minutes for 2 hours at each visit. There were 4 visits in each block each visit separated by 3-7 days. There were three blocks each block separated by 3-7 days.]

   The baseline FEV1 (before treatment) was subtracted from the maximum FEV1 recorded during the 2 h period following treatment. This difference value was then converted into percent improvement by dividing by baseline FEV1 and multiplying by 100. Each treatment was given 3 times to each patient, so we averaged the 3 values to yield the mean percent change in FEV1 for each condition.

Secondary Outcome Measures

1. Asthma Symptoms [Assesed over 2 hours during each visit. There were 4 visits in each block each visit separated by 3-7 days. There were three blocks each block separated by 3-7 days.]

   Subjective change in asthma symptoms on a visual-analogue scale with scores ranging from 0 (no positive change) to 10 (complete positive change). These subjective responses were then converted to percent change during the 2 hours by multiplying each score by 10. Each of these individual subject scores were then averaged to produce an average percent change in symptoms.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• uncontrolled asthma

Exclusion Criteria:

• no bronchodilator response

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Brigham & women's Hospital	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Brigham and Women's Hospital
• National Center for Complementary and Integrative Health (NCCIH)

Investigators

• Principal Investigator: Michael Wechsler, MD, Brigham and Women's Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Michael Wechsler, MD, Michael Wechsler, MD, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT01143688
• Other Study ID Numbers: 2005P-002045; R21AT002793-01; K24AT004095
• First Posted: Jun 14, 2010
• Last Update Posted: Mar 30, 2017
• Last Verified: Mar 1, 2017

• Additional relevant MeSH terms: Asthma; Albuterol

Study Results

Participant Flow

Pre-assignment Detail	79 patients completed questionnaires, 46 patients had reversibility and were randomized, and 39 completed the whole trial. The data was solely based on the 39 subjects who completed the entire trial.

Arm/Group Title	All Study Participants
Arm/Group Description	Each study participant was randomized to a specific random sequence of interventions for visits 1-4 (e.g. first inhaled bronchodilator, then inhaled placebo, then sham acupuncture, then no intervention administered 3-7 days apart, or first sham acupuncture, then inhaled bronchodilator, then no intervention, then inhaled placebo administered 3-7 days apart, or any other combination of these four interventions in any order). This process was repeated for visits 5-8 and again for visits 9-12.
Period Title: Overall Study
STARTED	39
COMPLETED	39
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Overall Study
Arm/Group Description
Overall Participants	46
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.5 (17)
Sex: Female, Male (Count of Participants)
Female	37 80.4%
Male	9 19.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	11 23.9%
White	28 60.9%
More than one race	0 0%
Unknown or Not Reported	7 15.2%

Outcome Measures

1. Primary Outcome

Title	Change in FEV1
Description	The baseline FEV1 (before treatment) was subtracted from the maximum FEV1 recorded during the 2 h period following treatment. This difference value was then converted into percent improvement by dividing by baseline FEV1 and multiplying by 100. Each treatment was given 3 times to each patient, so we averaged the 3 values to yield the mean percent change in FEV1 for each condition.
Time Frame	FEV1 was assessed every 20 minutes for 2 hours at each visit. There were 4 visits in each block each visit separated by 3-7 days. There were three blocks each block separated by 3-7 days.

Outcome Measure Data

Analysis Population Description

Each patient went through each treatment arm (albuterol, placebo inhaler, placebo acupuncture, and no-intervention) once in block 1, then again in block 2, and again in block 3, for a total of 12 interventions of the course of the study.

Arm/Group Title	Albuterol Inhaler	Placebo Inhaler	Placebo Acupuncture	No-intervention Control
Arm/Group Description	Subjects will perform baseline spirometry. Subsequently subjects will be shown an unmarked metered-dose inhaler device. This inhaler contains active albuterol (90 mcg/puff). The subjects will be reminded that this inhaler may contain either albuterol or placebo, and will complete questionnaires documenting their expectations for improvement in lung function with this treatment. Subsequently subjects will inhale 4 puffs (360 mcg) of albuterol administered from this inhaler via a spacing device. Spirometry will be obtained every 20 minutes post inhalation and the maximal FEV1 measured over the subsequent 120 minutes will be recorded as the post-intervention response on that visit. In the time period between spirometry, subjects will sit quietly in a separate waiting area.	Subjects will be shown an unmarked metered-dose inhaler similar to that used for bronchodilator testing. This placebo inhaler contains only propellant and inert ingredients (trichlorofluoromethane and dichlorodifluoromethane with lecithin). The subjects will be reminded that this inhaler may contain either albuterol or placebo. They will then inhale 4 puffs of the placebo inhaler containing only the propellant vehicle through a spacer. Spirometry will be obtained every 20 minutes post inhalation and the maximal FEV1 measured over the subsequent 120 minutes will be recorded as the post-intervention response on that visit. In the time period between spirometry, subjects will sit quietly in a separate waiting area.	Subjects will be instructed that they will receive one of three different acupuncture point combinations that may or may not be effective for asthma. Placebo acupuncture will be performed with a validated acupuncture device that allows patients to see an acupuncture needle enter their skin and actually feel the sensation of penetration. The needle penetrates up the needle shaft and never penetrates the point. The needle has been validated and shown to be indistinguishable from real acupuncture.	Subjects will be instructed that they will receive no interventions on this visit. Spirometry will be obtained every 20 minutes for maximal FEV1 for 120 minutes. In the time period between spirometry, subjects will sit quietly in a separate waiting area.
Measure Participants	39	39	39	39
Mean (Standard Error) [percentage change in FEV1]	20.1 (1.6)	7.5 (1.0)	7.3 (0.8)	7.1 (0.8)

2. Secondary Outcome

Title	Asthma Symptoms
Description	Subjective change in asthma symptoms on a visual-analogue scale with scores ranging from 0 (no positive change) to 10 (complete positive change). These subjective responses were then converted to percent change during the 2 hours by multiplying each score by 10. Each of these individual subject scores were then averaged to produce an average percent change in symptoms.
Time Frame	Assesed over 2 hours during each visit. There were 4 visits in each block each visit separated by 3-7 days. There were three blocks each block separated by 3-7 days.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Albuterol Inhaler	Placebo Inhaler	Placebo Acupuncture	No-intervention Control
Arm/Group Description	Subjects will perform baseline spirometry. Subsequently subjects will be shown an unmarked metered-dose inhaler device. This inhaler contains active albuterol (90 mcg/puff). The subjects will be reminded that this inhaler may contain either albuterol or placebo, and will complete questionnaires documenting their expectations for improvement in lung function with this treatment. Subsequently subjects will inhale 4 puffs (360 mcg) of albuterol administered from this inhaler via a spacing device. Spirometry will be obtained every 20 minutes post inhalation and the maximal FEV1 measured over the subsequent 120 minutes will be recorded as the post-intervention response on that visit. In the time period between spirometry, subjects will sit quietly in a separate waiting area.	Subjects will be shown an unmarked metered-dose inhaler similar to that used for bronchodilator testing. This placebo inhaler contains only propellant and inert ingredients (trichlorofluoromethane and dichlorodifluoromethane with lecithin). The subjects will be reminded that this inhaler may contain either albuterol or placebo. They will then inhale 4 puffs of the placebo inhaler containing only the propellant vehicle through a spacer. Spirometry will be obtained every 20 minutes post inhalation and the maximal FEV1 measured over the subsequent 120 minutes will be recorded as the post-intervention response on that visit. In the time period between spirometry, subjects will sit quietly in a separate waiting area.	Subjects will be instructed that they will receive one of three different acupuncture point combinations that may or may not be effective for asthma. Placebo acupuncture will be performed with a validated acupuncture device that allows patients to see an acupuncture needle enter their skin and actually feel the sensation of penetration. The needle penetrates up the needle shaft and never penetrates the point. The needle has been validated and shown to be indistinguishable from real acupuncture.	Subjects will be instructed that they will receive no interventions on this visit. Spirometry will be obtained every 20 minutes for maximal FEV1 for 120 minutes. In the time period between spirometry, subjects will sit quietly in a separate waiting area.
Measure Participants	39	39	39	39
Mean (Standard Error) [percent change in symptoms]	50 (3.75)	45 (3.75)	46 (3.75)	21 (3.45)

Adverse Events

Arm/Group Title	Albuterol Inhaler		Placebo Inhaler		Placebo Acupuncture		No-intervention Control
Arm/Group Description	Subjects will perform baseline spirometry. Subsequently subjects will be shown an unmarked metered-dose inhaler device. This inhaler contains active albuterol (90 mcg/puff). The subjects will be reminded that this inhaler may contain either albuterol or placebo, and will complete questionnaires documenting their expectations for improvement in lung function with this treatment. Subsequently subjects will inhale 4 puffs (360 mcg) of albuterol administered from this inhaler via a spacing device. Spirometry will be obtained every 20 minutes post inhalation and the maximal FEV1 measured over the subsequent 120 minutes will be recorded as the post-intervention response on that visit. In the time period between spirometry, subjects will sit quietly in a separate waiting area.		Subjects will be shown an unmarked metered-dose inhaler similar to that used for bronchodilator testing. This placebo inhaler contains only propellant and inert ingredients (trichlorofluoromethane and dichlorodifluoromethane with lecithin). The subjects will be reminded that this inhaler may contain either albuterol or placebo. They will then inhale 4 puffs of the placebo inhaler containing only the propellant vehicle through a spacer. Spirometry will be obtained every 20 minutes post inhalation and the maximal FEV1 measured over the subsequent 120 minutes will be recorded as the post-intervention response on that visit. In the time period between spirometry, subjects will sit quietly in a separate waiting area.		Subjects will be instructed that they will receive one of three different acupuncture point combinations that may or may not be effective for asthma. Placebo acupuncture will be performed with a validated acupuncture device that allows patients to see an acupuncture needle enter their skin and actually feel the sensation of penetration. The needle penetrates up the needle shaft and never penetrates the point. The needle has been validated and shown to be indistinguishable from real acupuncture.		Subjects will be instructed that they will receive no interventions on this visit. Spirometry will be obtained every 20 minutes for maximal FEV1 for 120 minutes. In the time period between spirometry, subjects will sit quietly in a separate waiting area.
All Cause Mortality
	Albuterol Inhaler		Placebo Inhaler		Placebo Acupuncture		No-intervention Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Albuterol Inhaler		Placebo Inhaler		Placebo Acupuncture		No-intervention Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/39 (0%)		0/39 (0%)		0/39 (0%)		0/39 (0%)
Other (Not Including Serious) Adverse Events
	Albuterol Inhaler		Placebo Inhaler		Placebo Acupuncture		No-intervention Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/39 (0%)		0/39 (0%)		0/39 (0%)		0/39 (0%)

Limitations/Caveats

The subjective scale did not encompass worsening of symptoms. Only studied acute asthmatic response, not chronic. Used single objective measure (FEV1) and single subjective measure. Did not assess subjective symptoms before each visit's intervention

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.