Pilot of Lifestyle and Asthma Intervention
Phase: NA
Conditions: Asthma
Sponsor: Johns Hopkins University

27 Mar 2020 
American Lung Association 
Airways Clinical Research Centers 
Pilot of Lifestyle and Asthma Intervention 
(PLAN) 
Protocol 
Version 1.4 
Supported by NIH grants: R34 HL136755 
NCT03291808
PI at University of Vermont: Anne Dixon, MD 
PI at Johns Hopkins: Robert Wise, MD

PLAN protocol version 1.4                                                                                                         Table of contents |1 
Confidential, not for attrition or citation. 
Table of contents 
1. Introduction .............................................................................................................................................. 3 
1.1. Background ........................................................................................................................................ 3 
1.2. Primary objective ............................................................................................................................... 3 
1.3. Secondary objective ........................................................................................................................... 3 
1.4. Overview of study design ................................................................................................................... 4 
2. Methods .................................................................................................................................................... 5 
2.1. Eligibility criteria................................................................................................................................. 5 
2.1.1. Inclusion criteria .......................................................................................................................... 5 
2.1.2. Exclusion criteria ......................................................................................................................... 5 
2.1.3. Rationale for eligibility criteria .................................................................................................... 5 
2.2. Asthma clinical assessments .............................................................................................................. 6 
2.3. Schedule of visits ................................................................................................................................ 7 
2.4. Weight loss intervention .................................................................................................................... 8 
2.4.1. Basic components of the weight loss program ........................................................................... 8 
2.4.2. Internet delivery of behavioral weight control program ............................................................ 9 
2.4.3. Promoting adherence to the online weight control intervention .............................................. 9 
2.4.4. Online weight control facilitator ............................................................................................... 10 
2.4.5. Intervention training and fidelity monitoring ........................................................................... 10 
2.4.6. Assembling weight control cohorts .......................................................................................... 10 
2.5. Statistical considerations ................................................................................................................. 11 
2.5.1. Data analysis ............................................................................................................................. 11 
2.5.2. Sample size ................................................................................................................................ 11 
2.5.3. Statistical methods .................................................................................................................... 12 
3. Monitoring .............................................................................................................................................. 13 
3.1. Composition of the Data and Safety Monitoring Plan (DSMB) ........................................................ 13 
3.2. Medical Monitor .............................................................................................................................. 13 
3.3. Monitoring procedures, frequency of monitoring, contents of DSMB report ................................ 13 
3.4. Adverse event and unanticipated event reporting .......................................................................... 13 
3.5. Changes/amendments to protocol or consent ................................................................................ 14 
3.6. Risks ................................................................................................................................................. 14 
3.6.1. Pulmonary function testing ...................................................................................................... 14 
3.6.2. Venipuncture ............................................................................................................................ 14 
3.6.3. Psychological and financial risks ............................................................................................... 14 
3.6.4. Exercise program ...................................................................................................................... 15 
3.6.5. Management of SAEs or other study risks ................................................................................ 15 
3.7. Potential benefits of the proposed research to human subjects and others .................................. 15 
3.8. IND/IDE information ........................................................................................................................ 15 
3.9. Conflicts of interest .......................................................................................................................... 15 
3.10. Data acquisition and transmission ................................................................................................. 15 
3.11. Stopping rules, interim analysis ..................................................................................................... 16 
3.12. Inclusion of women ........................................................................................................................ 16 

PLAN protocol version 1.4                                                                                                         Table of contents |2 
Confidential, not for attrition or citation. 
3.13. Inclusion of minorities ................................................................................................................... 16 
3.14. Inclusion of children ....................................................................................................................... 16 
4. References .............................................................................................................................................. 17 

PLAN protocol version 1.4                                                                                                                 Introduction |3 
Confidential, not for attrition or citation. 
1. Introduction 
 
The purpose of this protocol is to pilot test a weight loss intervention in obese patients with poorly 
controlled asthma. 
1.1. Background 
 
Obesity is a risk factor for the development of asthma (approximately 250,000 cases per year of asthma 
in the U.S. are related to obesity).1  Obese patients often have poorly controlled asthma (with a nearly 5-
fold risk of hospitalization compared with lean asthmatics) and do not respond as well to conventional 
controller therapy.2-6 Obesity particularly affects minority populations7: non-Hispanic blacks have the 
highest age-adjusted rates of obesity (47.8%) followed by Hispanics (42.5%), non-Hispanic whites 
(32.6%), and non-Hispanic Asians (10.8%).  This is thought to account in part for the disparities of 
asthma in minority populations.  There is a pressing public health need to develop interventions 
specifically for obese asthmatics. 
 
One obvious intervention to consider for treatment of obese asthmatics is weight loss.  Weight loss 
surgery significantly improves asthma-related outcomes.8-10  However, uncontrolled asthma increases 
surgical risk, and is an expensive, complex intervention only appropriate for a small subset of 
patients.11,12  Life-style interventions to promote weight loss in asthma may provide a simple, less 
expensive alternative, with the potential to reach a broader range of patients.  Single center studies 
suggest that diet-induced weight loss might improve asthma,13-16 but there have been no large 
multicenter clinical trials addressing the efficacy of weight loss in patients with poorly controlled 
asthma.17      
 
Our ultimate purpose is to test the hypothesis that weight loss through an intensive life style 
intervention will improve asthma control. But we first need to establish whether our weight loss 
intervention is effective in patients with asthma. 
1.2. Primary objective 
 
The primary objective of this study is to determine the effectiveness of an internet-based weight loss 
intervention in producing weight loss in obese patients with poorly controlled asthma. 
1.3. Secondary objective 
 
The ultimate purpose is to implement a multi-center weight loss intervention trial for obese patients 
with poorly controlled asthma. 
 
 

PLAN protocol version 1.4                                                                                                                 Introduction |4 
Confidential, not for attrition or citation. 
1.4. Overview of study design 
 
This will be a pilot study of a weight loss intervention at two centers, the University of Arizona and the 
University of Vermont.  The primary outcome of interest will be the percent of participants achieving a 
5% weight loss, which is the amount of weight loss that prior studies suggest is required to improve 
asthma control. 
 
This will be a single arm-phase II futility trial; the “futility” to be assessed is the ability to produce weight 
loss.  Such designs are widely used in efficiently informing decisions to proceed to Phase III clinical trials. 
This trial design is appropriate when the effect of the placebo arm can reasonably be estimated (weight 
loss is likely to be close to 0), and the toxicity of the treatment is minimal (no toxicity is anticipated 
related to weight loss).18  Therefore, this will be a single arm 6-month study of 40 participants (20 at 
each site). All participants will be assigned to the weight loss intervention, which is described in detail 
below.

PLAN protocol version 1.4                                                                                                                        Methods |5 
Confidential, not for attrition or citation. 
2. Methods 
2.1. Eligibility criteria 
2.1.1. Inclusion criteria  
 
 
Physician diagnosis of asthma on regular controller therapy for at least the past 3 months 
 
Age: ≥18 years of age 
 
Obese: BMI > 30 kg/m2 
 
Poorly controlled asthma 
 
Asthma Control Test Score ≤ 19,19,20 or  
 
use of rescue inhaler on average > 2 uses/week for preceding month, or  
 
nocturnal asthma awakening on average 1 or more times / week in preceding month, or  
 
ED/hospital visit or prednisone course for asthma in past six months 
 
Ability and willingness to provide informed consent 
 
Ability to access internet weight loss program for a trial period 
 
Completion of asthma, food and weight diary entries for same 3 consecutive days between visits 
1 and 2  
2.1.2. Exclusion criteria  
 
 
History of bariatric surgery  
 
Participant currently on weight loss drugs  
 
Any condition that puts the participant at risk from participation in a weight loss study or a 
condition that precludes participation in regular exercise as judged by the site physician 
 
Pregnancy (by patient self-report) 
 
Participation in another weight loss intervention within the last month 
 
Weight loss of ≥ 10 pounds in the last 6 months by self-report 
 
Intention to move out of area within the next 6 months 
2.1.3. Rationale for eligibility criteria 
 
Our goal is to enroll obese adults with asthma on asthma controller drugs. Enrollment criteria are 
purposely broad to ensure that the study population broadly reflects individuals who may be eligible for 
a weight loss intervention in a general medical setting.   We are not excluding people who have co-
morbid conditions or who smoke insofar as these individuals may benefit from the weight loss.  
 
 

PLAN protocol version 1.4                                                                                                                     Methods |6 
Confidential, not for attrition or citation. 
2.2. Asthma clinical assessments 
 
Patients will undergo spirometry with post-bronchodilator reversibility testing at 0 weeks and 24 weeks, 
spirometry at all other visits will be done without bronchodilator administration. Questionnaires and 
diary entries will be available in English and Spanish.  
 
Asthma diaries on the PLAN website will be completed by participants throughout the study to 
record daily morning peak expiratory flow (PEF), daily asthma symptom scores, beta-agonist 
use, nocturnal asthma awakenings, and health care use.  Diary data are used to identify 
episodes of poor asthma control and days with no asthma symptoms (asthma-free days). 
 
The Asthma Control Test (ACT) is a 4-week recall questionnaire that measures asthma control.19  
 
The Asthma Symptom Utility Index (ASUI) is a 2-week utility-weighted asthma symptom 
questionnaire.21  
 
The Marks Asthma Quality of Life Questionnaire (Marks AQLQ) assesses asthma specific quality 
of life.22  
 
Medical Outcomes Study (SF36v1) is a measure of general health related quality of life which 
correlates with asthma outcomes.  
 
The IWQOL-lite is used to measure the effect of weight loss on QOL.23  
 
Food Frequency,24 activity25 and motivation to lose weight26, will be assessed using validated 
questionnaires. 
 
Anthropometrics will include height, weight, waist, hip circumference per NHANES III.  
 
For subjects who have not been seen in the pulmonary clinic in the last 12 months will have a 
brief physical exam at visit 2.  
 
Spirometry will be performed in accordance with ATS/ERS guidelines.27  
 
Adverse effects will be assessed by open-ended questions at each visit and rated in severity.  
 
Interval health history will be recorded at each clinic visit. Records of all hospitalizations and, if 
necessary, deaths are obtained for verification of diagnoses and assessment of safety issues. 
 
Participants will be asked if they are pregnant at every visit, and if they become pregnant, they 
will be withdrawn from the study.  
 
Baseline questionnaires and exam will be administered to ascertain demographics Including self-
reported ethnicity and race, general health, co-morbid conditions, asthma symptoms, and 
medication use. Medical clearance for diet and moderate exercise will be provided by the study 
site physician.  
 
Exit questionnaires will be administered at the last visit to determine global assessments of 
treatment, adequacy of informed consent procedures, satisfaction with study procedures and 
personnel, and opinions about the intervention. 
 
Blood specimens will be collected for fasting blood glucose and analysis of metabolic and 
oxidative markers related to asthma. Excess blood specimens will be used for future asthma 
research with the patient’s consent. Fasting blood draw may take place within 7 days of rest of 
the procedures scheduled for visit 2 or visit 6. 
 
 

PLAN protocol version 1.4                                                                                                                     Methods |7 
Confidential, not for attrition or citation. 
2.3. Schedule of visits 
 
Visit Number 
V1 
V2 
N 
- 
P1ǂ 
V3 
V4 
V5 
V6 
Time (week) 
 
-2 
 
0 
2 
6 
12 
18 
24 
Informed Consent 
• 
 
 
 
 
 
 
 
 
Medical History 
• 
• 
 
 
 
• 
• 
• 
• 
Interim Body Weight 
Measurement 
 
 
• 
 
 
 
 
 
 
Orientation to weight loss 
program 
• 
• 
 
 
 
 
 
 
 
Start Weight Loss Program 
 
 
 
• 
 
 
 
 
 
Provision of Chromebook 
computer 
 
• 
 
 
 
 
 
 
 
Addressing website login issues 
and exercise strategies/concerns 
at home; facilitator contact 
 
 
 
 
• 
 
 
 
 
Assessment of compliance with 
food, asthma and weight  diaries 
 
• 
 
 
 
 
 
 
 
Assessment of diary entry 
compliance 
 
• 
 
 
 
• 
• 
• 
• 
Spirometry  
• 
•¥ 
 
 
 
• 
• 
• 
•¥ 
Asthma Control (ACT and ASUI) 
• 
• 
 
 
 
• 
• 
• 
• 
Marks Asthma Quality of Life 
• 
• 
 
 
 
• 
• 
• 
• 
Quality of Life (SF36v1) 
• 
• 
 
 
 
 
 
 
• 
Arizona Food Frequency 
Questionnaire 
• 
 
 
 
 
 
 
 
• 
Stanford Brief Activity 
Questionnaire 
• 
 
 
 
 
 
 
 
• 
Impact of Weight on Quality of 
Life 
• 
 
 
 
 
 
 
 
• 
Motivation to lose weight (Tre-
MORE) 
• 
 
 
 
 
 
 
 
 
Height (V1 only), Weight, Hip and 
Waist Circumference 
• 
• 
 
 
 
• 
• 
• 
• 
Blood draw (fasting) 
 
• 
 
 
 
 
 
 
• 
End of Study Questionnaire 
 
 
 
 
 
 
 
 
• 
ǂThe purpose of P1 is to check in the participant to make sure they have made contact with the weight 
loss facilitator, and are not having technical problems with the website, or with MyFitnessPal. 
¥Spirometry at V2 and V6 will be pre and post bronchodilator, all other visits spirometry without 
bronchodilator.  
 
 

PLAN protocol version 1.4                                                                                                                     Methods |8 
Confidential, not for attrition or citation. 
2.4. Weight loss intervention 
 
The weight loss intervention will be implemented under the direction of Dr. Jean Harvey (Chair of 
Nutrition at UVM).  Participants will be introduced to the weight loss program during visit 1. A research 
coordinator will show participants how to access the weight loss website, the MyFitnessPal program, 
and provide information to contact the assigned weight loss coach. The participant’s picture will be 
taken to display on the chat page and on the biography page for their group when they use the study 
web site. Participants may opt out of this feature if they are uncomfortable having their picture 
displayed. 
 
After visit 1, participants will be asked to enter information on the weight loss website and the 
MyFitnessPal program to display that they understand how to use the programs. Participants will have a 
3-day trial period to enter daily asthma symptoms, food intake and exercise information online. The 
research team will assess completion of this trial period; only participants who enter complete diaries 
for same 3 consecutive days will be eligible to enroll in the study.  
We will attempt to enroll participants into this study in groups of 5-10 to provide an adequate group for 
the weight loss intervention.   
2.4.1. Basic components of the weight loss program  
 
This 6-month intervention will include restricted calorie intake and increased physical activity.  Key 
behavioral strategies to facilitate changes in dietary habits and activity patterns will be introduced, 
promoted and reinforced throughout the program.  Weekly “group meetings” in a synchronous chat 
(i.e., in real time) led by a facilitator will be the venue for the group process.  Extensive web-based 
resources to support behavior changes will be offered. The online groups will be “closed” such that 
those individuals who start the group remain in that group for the duration of their participation. Group 
chat sessions will meet online weekly for 6 months. 
 
1. Diet  
A balanced reduced calorie deficit diet will be prescribed.  All participants will be given an 
individualized calorie goal. Emphasis will be placed on consuming a diet high in fruits, 
vegetables, and whole grains, and low in fat, sugar, salt and alcohol.  Participants are asked to 
target fat intake to 25% of their overall calorie goal because a number of studies 28,29 suggest 
superior weight loss when fat and calories are both controlled.   
 
Participants will record their daily calorie and fat intake daily electronically.  They will have 
access on the study website to calorie and fat gram guides which use pull down menus and 
personally customized calorie/fat counters to facilitate ease of recording. The interventionist 
will reviews this diaries weekly and provide feedback to reinforce or shape new behaviors. 
 
2. Exercise  
Participants will be provided with graded goals to reach the recommended weekly minimum of 
200 minutes of moderate intensity exercise by week 9 of the program. We will recommend brisk 
walking as in our previous studies. At visit 1, we will verify they have a safe place to exercise as 
in our previous studies, other forms of aerobic exercise will also be encouraged should the 
participant prefer. All exercise will be monitored using electronic diaries that include pull down 
menus for a wide range of activities.   

PLAN protocol version 1.4                                                                                                                     Methods |9 
Confidential, not for attrition or citation. 
3. Behavioral strategies 
The major features of the behavior modification strategies in the program are based on Social 
Cognitive Theory30 and are described below.  Dr. Thomson and Vega-Lopez will be involved in 
training the bilingual lifestyle coach in cultural adaptation for Hispanic participants. 
2.4.2. Internet delivery of behavioral weight control program 
 
Participants will have access to behavioral lessons weekly.  The standard version of the lesson is very 
visual, capitalizing on the capabilities of the internet delivery.  We will be notified over the Web site 
when participants have completed lessons and we will, therefore, be able to electronically assess 
compliance with this program component 
 
All potential participants will be given an orientation to the website and MyFitnessPal at Visit 1 prior to 
entering the weight loss program.  We will assess compliance with asthma and food diary entries at Visit 
2, only participants who have completed diary requirements (same 3 days of asthma and food diaries) 
will be considered eligible to continue in study. 
 
Participants will be enrolled into a “group” at Visit 2, although they will not meet in-person and this 
“group” will be maintained throughout an individual’s study participation.  Groups will be homogenous 
with respect to language (English of Spanish).  Participants will have access to the Internet site and will 
be assigned a group on-line chat time.  The group facilitator will e-mail them weekly, and they will be 
encouraged to use various components of the Web site.  Individual usage of the site will be tracked by 
username through server activity logging and the use of WebTrends (NetIQ Corporation, San Jose, CA) 
log analysis software.  
 
Participants will have access to new behavioral lessons each week. Participants will be provided with a 
computer. We will provide them with a data plan or hot-spot for internet access if they do not have 
internet access.  
2.4.3. Promoting adherence to the online weight control intervention 
 
We encourage adherence by tailoring the intervention expectations to shape an individual’s behavior 
such that it approaches the intervention goals.  For example, individuals who are having difficulty self-
monitoring are given options to make it easier, walking them through how to develop their own 
shortcuts to self-monitoring (the “my pantry” option on the website), having a short term goal of 
recording just a few days a week or only specific meals of the day, etc.  Individuals who miss a group 
chat session will be contacted by email promptly.  Lesson materials are available for those who miss the 
chat, and summaries of the missed session.  We use a problem-solving approach to barriers to 
attendance. We have found this comprehensive and proactive approach to adherence promotion to be 
effective in maintaining high levels of study participation.   
 
 

PLAN protocol version 1.4                                                                                                                     Methods |10 
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2.4.4. Online weight control facilitator 
 
Dr. Harvey has trained a cadre of experienced facilitators who have conducted the online weight control 
program.  Online weight control interventionists on our research team at present include registered 
dieticians, masters-level health behavior experts, and doctoral level psychologists.  Thus, our online 
intervention team is multi-disciplinary, skilled in conducting behavioral weight loss treatment programs, 
and ethnically diverse.  The interventionist will be directly supervised by Dr. Harvey.  
2.4.5. Intervention training and fidelity monitoring  
 
Our previous experience in obesity treatment outcome research suggests that the following quality 
procedures will help ensure treatment fidelity:  
 
1. Development of detailed intervention protocols;  
2. Careful training, certification, and periodic re-training;  
3. Periodic observation of intervention delivery to ensure protocol adherence and to provide 
corrective feedback;  
4. Documentation of all intervention contacts to monitor participant exposure to treatment; and  
5. Regular project meetings to review overall conformity to structured protocols and prevent any 
drift between interventionists.   
2.4.6. Assembling weight control cohorts 
 
The intervention requires that 5-10 participants form a group to participate in the weekly group chat 
sessions. A group may include participants from both sites. The group will essentially be a cohort of 
participants starting and ending the study at the same time.  Because it is essential that the V1 and V2 
visits be conducted close together, the cohorts need to be assembled prior to starting the study. 
Individuals who are interested in the study will be directed to the PLAN website to complete a study 
registrations form. The form will include individuals’ names, contact information, basic eligibility 
information, information on the days of the week and times that a person will be consistently available 
for group chat sessions, preferred language (English or Spanish), and the center. These data may be 
collected prior to an individual providing consent for the study. The registration form will include text 
briefly describing study and how the information provided on the registration form will be used. Clinical 
center personnel will only be able to see the data from individuals who selected their center for 
attending study visits. The central coordinator will be able to view registration data from both sites in 
order to assemble the cohorts of 5-10 individuals who can participate in group chats at the same time. 
Once there are sufficient individuals who can participate in group chats at the same or similar times, the 
central coordinator will contact the clinical center coordinator to schedule V1 and V2 visits for these 
individuals.  If the individual has not provided consent, consent will be obtained at the V1 visit before 
screening. Once all the cohort has completed V2, the coaches will contact cohort members to schedule 
the first chat. The goal is for the first chat session to take place in the 2 weeks following V2. 
 
 

PLAN protocol version 1.4                                                                                                                     Methods |11 
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2.5. Statistical considerations 
2.5.1. Data analysis 
 
The appropriateness of the human, technological and systems components of the data acquisition and 
management procedures will be analyzed including practicality of data acquisition, estimation of likely 
participant characteristic and outcome distributions, suitability and functionality of paper and electronic 
forms, and resources required for participants contact and follow up, and to anticipate rates for missing 
data. Secondary analyses will include adjustments for different degrees of self-reported exercise. 
2.5.2. Sample size 
 
The decision to proceed to the full scale trial will be based on a futility design analysis, which guided our 
sample size estimates. We will determine this study as futile if we cannot produce a clinically significant 
weight loss in a significant proportion of participants. A clinically significant weight loss is set at 5% 
(which is the amount of weight that appears to be necessary to improve asthma control based on 
previous studies, and also the amount of weight loss required for FDA approval of a weight loss 
medication). A significant proportion of the population is set at 35% (FDA recommend that a weight loss 
medication must produce a 5% weight loss in 35% of participants to be considered effective).31   
 
A straightforward way to test for futility with a binary outcome is based on the binomial distribution32. 
For a given minimum sufficient efficacy (p1) and level that would indicate the intervention was 
ineffective (po), the threshold for continuing, c, can be determined for any sample size, n, as follows: the 
largest value of c such that P(X  c| po)  , type I error, and P(X  c| p1)  1-, power, i.e. minimize the 
type II error. Ineffective thresholds of 5% and 10% were considered (Table 2). To be conservative, drop-
outs will count as weight loss failures. With 40 patients, we have 94% power and  < 0.001 using a 
threshold of 9 and assuming po.= 0.1 vs p1 = 0.35, i.e. if 9 individuals have clinically significant weight 
loss we would reject futility and continue on to a larger trial. For the 12 Hispanics, we would need 3 ( 
= 0.026, 1- = 0.87) and 2 ( = 0.02, 1- = 0.85) individuals to achieve 5% weight loss reject futility 
assuming po.= 0.1 vs p1 = 0.45 and po.= 0.05 vs p1 = 0.35, respectively.  
 
Table 2: Power, type I error, and threshold for rejecting futility for a variety of futility, p0, and 
minimum efficacy, p1, thresholds 
po 
p1 
c 
N = 40 
, 1- 
po 
p1 
C 
N = 12 
C, , 1- 
0.1 
0.25 
6 
7 
8 
0.013, 0.96 
0.003, 0.90 
< 0.001, 0.82 
0.10 
0.40 
2 
3 
4 
0.11, 0.92 
0.026, 0.77 
0.004, 0.56 
 
0.30 
7 
8 
9 
< 0.001, 0.94 
< 0.001, 0.89 
< 0.001, 0.80 
 
0.45 
2 
3 
4 
0.11, 0.96 
0.026, 0.87 
0.004, 0.70 
 
0.35 
9 
10 
11 
< 0.001, 0.94 
< 0.001, 0.88 
< 0.001, 0.79 
0.05 
0.35 
1 
2 
3 
0.12, 0.96 
0.020, 0.85 
0.002, 0.65 
 
 

PLAN protocol version 1.4                                                                                                                     Methods |12 
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2.5.3. Statistical methods 
 
Descriptive statistics will be generated for all study parameters (e.g. SD of change in ACT). Cross-
sectional comparisons will be made using Kruskall-Wallis and Fisher’s exact tests.  We will determine the 
proportion of participants achieving a 5% weight loss with exact 95% confidence intervals.  Mixed effects 
models will be used to analyze repeated measures.    

PLAN protocol version 1.4                                                                                                                 Monitoring |13 
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3. Monitoring  
3.1. Composition of the Data and Safety Monitoring Plan (DSMB) 
 
Significant changes or amendments to the protocol or consent form will be submitted to the DSMB, and 
included in the DSMB reports. 
 
The American Lung Association appoints a DSMB to oversee trials conducted by the ACRC. The primary 
responsibility of the DSMB is to protect participants but may also have recommendations regarding the 
scientific conduct of the study to optimize the risk-benefit ratio for participants. The DSMB is typically 
composed of a pulmonary specialist, an ethicist, a statistician, a patient representative, and specific 
content experts which in this case would likely be a nutritionist or health psychologist.  
3.2. Medical Monitor 
 
Dr. Wise at Johns Hopkins serves as the medical monitor for the ALA-ACRC research group and reviews 
all serious adverse event or unusual event reports to determine whether any immediate local or study-
wide actions are indicated. Interim serious adverse events or adverse events related to study 
procedures are transmitted to the DSMB by the DCC with concurrent notification of the clinical site IRBs 
and, if appropriate, NIH.  
3.3. Monitoring procedures, frequency of monitoring, contents of 
DSMB report 
 
Typically, the DSMB would have an initial meeting to review and approve the protocol, and then meet 
every six months or more frequently to review the progress of the trial. The investigators present the 
DSMB study performance data including screening and enrollment data, and measures of data quality 
and timeliness. Safety data will include reporting of adverse events, protocol deviations, and unexpected 
or unanticipated problems that may affect the safety or scientific validity of the study.  
 
At the end of each DSMB meeting, the board will vote whether to continue the study as planned or 
whether to recommend changes to the study. The DSMB may recommend that the study be stopped 
early if there is evidence that the risk-benefit ratio does not warrant continuation of the trial.  
3.4. Adverse event and unanticipated event reporting 
 
The site PI will submit a completed serious adverse event report to the DCC and the IRB, and then the 
DCC will report to the NIH, and Chair of the DSMB within 7 days of the report of a potentially life-
threatening (grade 4) or severe (grade 3) serious adverse event that is possibly, probably or definitely 
related to the study. 
 
The PI will report to the DCC and the IRB, and the DCC will report to the NIH, FDA and DSMP within 15 
days of any other event or condition regardless of grade, which in their judgment represents an event 
reportable to the IRB, NIH, FDA and DSMP. 
 
A summary of all adverse events will be reported to the DSMP, NIH, and IRB at least annually. 

PLAN protocol version 1.4                                                                                                                 Monitoring |14 
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3.5. Changes/amendments to protocol or consent 
 
Significant changes or amendments to the protocol or consent form will be submitted to the DSMB, and 
included in the DSMB reports. 
3.6. Risks 
 
Participation in this research protocol requires routine clinical procedures that entail more than minimal 
risk. The registration database will contain personal identifiers and be stored at the DCC. Access to those 
data will be restricted to the database manager and the coordinator(s) responsible for assembling 
cohorts.  Data are stored on servers that are maintained behind an institutional firewall.  All portions of 
the data system will be password-protected using a standard challenge/response system coupled with a 
second user-specific identity system requiring users to log in with their personal PIN and strong 
password, which are checked before the login is completed.  Once the user is logged in, all subsequent 
activities are stamped with the user’s PIN and date-time stamp. 
3.6.1. Pulmonary function testing  
 
Pulmonary function testing requires deep and forceful respiratory efforts. It is a commonly performed 
and safe examination that is widely performed in patients with lung disorders. Some patients report 
chest soreness the day following the procedure. Some patients may experience light-headedness during 
the forced expiration. The risk of syncope is mitigated by having the patient perform the test in the 
seated rather than standing position. Spirometry will also be performed with a bronchodilator on visits 2 
and 7. On rare occasions (less than 5% of the time), bronchodilators may cause nervousness, a rapid 
heartbeat or headache at the doses used in this study. If you develop any of these problems, we will 
monitor you closely until the problem goes away (typically in 30 minutes).  
3.6.2. Venipuncture 
 
Venipuncture may cause bruising and minor discomfort. Abnormal fasting blood glucose levels will be 
communicated to participants and, with their permission, their primary care physician. 
3.6.3. Psychological and financial risks 
 
Psychological or financial risks are unlikely, but there may be unforeseen psychological or financial risks 
for participants in this trial. For example, patients may have unrealistic expectations of benefit from 
treatment received in a trial, or may have psychological distress from having a diagnosis of asthma or 
other concomitant diseases discovered during screening evaluation. Patients may also have financial loss 
from their occupations to attend clinic visits. Many patients, however, receive psychological benefit 
from participating in a study that may help others, and the financial costs are mitigated by small 
honoraria for participation in the study. 
 
 

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3.6.4. Exercise program 
 
Exercise Program potential risks may include the participant  not being able to identify a safe place to 
exercise, or having physical impediments to exercise.  We will try to help participants identify a safe 
place to exercise.  We will exclude participants who the site physician determines are physically unable 
to participate in a regular (typically walking-based) exercise program. 
 
Participation in a weight loss program: The participant might not be able to identify a safe place to 
exercise, or have physical impediments to exercise.  We will try to help participants identify a safe place 
to exercise. We will exclude participants who the site physician determines is physically unable to 
participate in a regular (typically walking-based) exercise program. 
3.6.5. Management of SAEs or other study risks  
 
We will follow our standard IRB procedures for following SAE’s, and reporting procedures as outlined 
above. 
3.7. Potential benefits of the proposed research to human subjects 
and others  
 
Patients will benefit from asthma education and attention to their asthma care program. Some obese 
patients may achieve weight loss which is generally considered healthy. If this program is successful, it 
will provide evidence to support a new approach to the treatment of poorly controlled asthma in obese 
patients with particular emphasis on minorities. Moreover, some participants in research studies report 
that they enjoy participation because they have the opportunity to assist in the development of new 
knowledge that may be helpful to others and that the relationship with the research staff is rewarding.  
3.8. IND/IDE information 
 
Not applicable 
3.9. Conflicts of interest 
 
We will follow the ALA ACRC annual reporting requirements for management of conflict of interest. 
3.10. Data acquisition and transmission 
 
The research team at the study site will collect information directly from the participant, recorded with 
full Identifiers. Data collected at study visits will be identified with a study ID and alpha code, assigned 
by the clinic coordinator so that personal identifiers are not keyed into the study database.  However, 
the registration database, which will be used to assemble the cohorts, will have personal identifiers.  
The registration database will not contain the study ID’s assigned to enrolled participants so that the 
personal identifiers cannot be linked with the study data at the DCC.  
   

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3.11. Stopping rules, interim analysis 
 
Patients may withdraw from the study at any time. 
 
There are no plans for interim outcome data analysis for this pilot study. 
3.12. Inclusion of women  
 
Both women and men will be enrolled in these studies. Asthma is more prevalent among female adults, 
and so we anticipate a slight majority of participants will be women. 
3.13. Inclusion of minorities  
 
We anticipate Vermont and Arizona will reflect the demographics of these two regions, and anticipate 
recruiting a high proportion of Hispanics at the Arizona site. 
3.14. Inclusion of children 
 
We will not include children under 18 years of age, as weight loss in children will require a specific 
family-centered intervention, and so differ from the type of intervention that we will be using in adults.  
Asthma and obesity are obviously important medical issues in younger children, and so our network is 
working to develop a separate study specifically to target obesity in younger asthmatics. 
 

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