Physical Activity Intervention for Urban Black Women With Asthma: Protocol for a Randomized Controlled Efficacy Study

Background Black women experience a higher prevalence of poor asthma outcomes and physical inactivity than their White counterparts. Black women comprise a particularly vulnerable group of patients with asthma, with some of the highest rates of asthma in adults, high health care use (emergency department visits and hospitalizations), and the highest crude asthma mortality rate of all race or ethnicity groups. Despite recommendations to engage in regular physical activity, fewer than 15% of Black women meet the 2008 National Physical Activity Guidelines, the lowest of all racial subgroups of adults. Given the connection between physical inactivity and poor asthma outcomes, addressing physical activity among Black women with asthma is imperative. Objective This 2-arm randomized controlled trial aims to (1) determine the efficacy of a lifestyle walking intervention on asthma control compared to an education (control) group over 24 weeks, (2) examine the maintenance effects of the lifestyle walking intervention on asthma control at 48 weeks, (3) explore the behavioral mediators (eg, self-efficacy, social support, self-regulation, and daily physical activity levels) and contextual moderators (eg, baseline asthma severity, neighborhood environment, comorbid conditions, and social determinants of health) that contribute to treatment responsiveness, and (4) assess the reach and implementation potential of the intervention. Methods The proposed study (ACTION [A Lifestyle Physical Activity Intervention for Minority Women with Asthma]) delivers a 24-week lifestyle walking intervention designed for and by urban Black women with asthma. Participants (n=224) will be recruited through 2 urban health care systems that care for a diverse Black population. Patients will be randomized to one of two groups: (1) ACTION intervention (group sessions, physical activity self-monitoring—Fitbit, and text-based support for step goal setting) or (2) education control (an individual asthma education session and SMS text messages related to asthma education). Outcome assessments will take place at baseline, 12, 24, and 48 weeks. The primary outcome is a change in asthma control from baseline to week 24 as assessed by the asthma control questionnaire-6 (ACQ-6). Secondary outcomes include asthma-related quality of life, health care use, and asthma exacerbations and behavioral outcomes such as self-efficacy, self-regulation, social support, and physical activity. Results This study was funded by the National Institute of Minority Health Disparities in August 2022. We pilot-tested our recruitment and intervention procedures and began recruitment in April 2023, with the enrollment of our first participant in May 2023. The anticipated completion of the study is April 2027. Conclusions This study will deliver a new approach to physical activity interventions in Black women with asthma and help to provide guidance for addressing physical activity within this subgroup. This study will also provide a potential framework for future studies in minoritized populations with other disease conditions associated with low levels of physical activity. Trial Registration ClinicalTrials.gov NCT05726487; https://clinicaltrials.gov/study/NCT05726487 International Registered Report Identifier (IRRID) DERR1-10.2196/55700

implementation potential of ACTION (A lifestyle physiCal acTivity Intervention for minOrity womeN with asthma) to increase physical activity and asthma health outcomes to reduce the burden of asthma in African American women.

CRITIQUE 1
Significance: 1 Investigator(s): 2 Innovation: 1 Approach: 3 Environment: 1 Overall Impact: This RCT will test the efficacy and implementation potential of ACTION (A lifestyle physical acTivity Intervention for minOrity womeN with asthma) to increase physical activity and asthma health outcomes to reduce the burden of asthma in 224 African American women.The main hypothesis is that the 24-week intervention (ACTION) will lead to a significant improvement in asthma control that will be maintained at 48-weeks with a less intensive intervention.Aims 1 and 3 are independent and complementary.Importantly Aim3, will provide insight regarding implementation of the intervention, which can have a great public health impact.The research team is strong and well-rounded, the environment is well-suited for such a trial, and the approach is overall sound.There are some weaknesses/missed opportunities mostly related to Aim 2 that could be easily addressed.In summary, the overall impact of this application is strong.

Strengths
• This RCT is well-aligned with the K award goals and seems to be a natural continuation of the K work • Preliminary data regarding asthma control and some mediators is strong • A patient-centric intervention specifically targeting AA women is long due • Data and methods derived from this RCT could be applied to other outcomes affected by sedentarism, such as cardiometabolic risk and the like

Weaknesses
• None noted

Strengths
• The PI piloted the exercise program during her K award

Weaknesses
• This is an observation, not a real weakness: PI's total effort for this project is 28% and not 35% as listed.

Strengths
• A multi-faceted affordable physical activity intervention for a minority group at risk is novel • Great use of mobile health and remote health coaching.This a thoughtful approach to reduce participants' burden and promote social distancing in these times • iCardia platform is innovative and might be able to develop other uses during the duration of this trial

Weaknesses
• None noted

Strengths
• Well thought-out trial deployment • Sound sample size calculation and attrition estimation.Hence, the proposed sample size is feasible • Strong Aim 1 with high possibilities of panning out • Strong and needed Aim 3, very important from a public health standpoint

Weaknesses
• Aim 2 involves several explorations and hence, is subject to potential pitfalls as described below • Interventionists and remote health coaches can add variability to the intervention.Will a remediation plan be instituted if needed?These factors should also be considered as moderators in the statistical plan • Along the same lines, can text messages be standardized?
• Will seasons be incorporated into the analyses and/or randomization schedule?
• Minor: I know this is not a sleep-focused grant but it would be important to add one questionnaire about OSA and one about sleep quality as both can mediate exercise, can be affected by asthma, and OSA is not an exclusion criteria.In fact, some participants may be treated with CPAP.This could be an exploratory aim hypothesizing that sleep quality would improve in the intervention group.Easy to solve missed opportunity • I understand the constraints of longer trials, but it would be important to explore sustainability of findings by continuing tracking steps 6 months after the end of the trial for example, and correlate these findings with asthma control tools 5. Environment: • UIC has a strong system to foster tis research.This includes the Center for Clinical and Translational Science, the Bioinformatics core, mHealth lab, and a vast clinical population • UC also has a vast clinical population to support this research Overall Impact: Rates of physical inactivity, asthma, and asthma mortality among African American (AA) women are higher than those of their White counterparts The investigators propose a 24-week theory-driven lifestyle physical activity intervention designed for and by urban AA women with asthma.
The proposed study has the potential to have a significant scientific impact by advancing clinical treatment of asthma, and furthering the behavioral mechanistic understanding of PA interventions in minority populations living with asthma.The intervention has a strong theoretical framework and is based on preliminary data from the same investigatory team.The investigatory team is heavy with physicians, with a strong biomedical perspective.The study design could be strengthened by the addition of an investigator with experience in women's studies-this would ensure consideration of the norms, values, and the meanings of and the barriers that societies impose on women and their health promotion needs.There are also questions about the potential for contamination of the Experimental and Control groups and how this can be avoided.

Strengths
• Investigatory team has preliminary data from prior studies that provide a solid premise for conducting this efficacy trial of a PA intervention targeting African American women with asthma • Intervention is based upon social cognitive theory and augmented by self-regulation theory.

Weaknesses
• Since walking is the principal form of physical activity, have seasonal effects been considered in the design of the study?Chicago winters are cold!

Strengths
• PI is a new investigator who recently finished a K award, which was the basis for the proposed study • Investigatory team members share a track-record of collaboration, as evidenced by many funded grant proposals and publications.This is an intradisciplinary team composed of experts in pulmonary medicine, biomedical and health informatics, epidemiology, biostatistics and behavioral science.

Weaknesses
• Three of the investigators (including the PI) are physicians, implying that this proposal likely comes from a strong biomedical perspective.Given that the intervention will be targeting women, I would argue for some epistemological diversity.It would be helpful to have someone with a background in women's studies to put the experiences and situations of women attempting to exercise within historical, gender, and social contexts.This will inform the intervention to include a consideration of the norms, values, and the meanings of and the barriers that societies impose on women and their health promotion needs.

Strengths
• Intervention includes text-based goal-setting with a remote health coach to enhance the PA intervention Weaknesses • None noted 4. Approach:

Strengths
• The investigators are proposing an efficacy study that focuses on asthma outcomes, explores behavioral mechanisms of the intervention, and assesses factors that influence its reach and implementation potential.
• Reach of the proposed intervention will be measured by the number of potential participants (based on the recruitment pool) who are randomized into the study.Implementation potential will be measured using a mixed methods approach to identify important explanatory factors underlying the performance of the intervention components.
• Physical activity ill be tracked by accelerometry • Team plans to recruit a total of 224 subjects-112 participants in each group.This will assume an attrition rate of 25% from the pilot study.Weaknesses shown to increase PA in other contexts.The focus on implementation outcomes will help to propel this work forward after the completion of this study.The research team is excellent.The PI has conducted a pilot study of the proposed intervention, and has refined and expanded the intervention based on participant feedback.Investigators include many design features that support rigor of the science.Overall this was a strong application, but I did have some concerns about the study.Most significant concerns are outlined here.First, investigators provide few details on how the intervention was tailored to African American women.Provision of this information would help to justify having an intervention specifically targeted toward this demographic group.Second, there was no theory or hypotheses presented about why increased PA would lead to better asthma control.Third, investigators should use the PHQ-9 rather than the PHQ-8 unless there is a very strong rationale.From a human subjects perspective, it is better to ask about suicide --as that gives researchers an opportunity to intervene and provide necessary referrals or resources.Fourth, the study should be powered to detect a minimally clinically important differences that is specific to the outcome of interest (asthma control), not general.Power analyses also should not be based on effect sizes from pilot data which likely have a wide confidence interval around them.Finally, there was no institutional information included about the University of Chicago site.Overall, I thought this study has the potential to have a substantive impact if these concerns were adequately addressed.

Strengths
• African American women have high rates of asthma and low rates of physical activity.People with asthma experience unique barriers to physical activity including fear related to experiences with asthma exacerbations.Previous research has shown that PA interventions are safe and improve asthma-related outcomes.Thus, there is a rationale for using a PA intervention to increase PA an improve asthma control in African American women.
• Investigators are planning to examine efficacy during the active intervention period (24 weeks) as well as maintenance of gains 24 weeks later.
• Investigators plan to investigate increased PA as a mediator of the primary outcome of asthma control.
• Investigators plan to assess implementation outcomes in order to plan for a future scale-up.

Weaknesses
• Investigators do not provide any details on how this intervention was tailored specifically for African American women, other than the fact that the interventionists will be African American women.Providing this information would strengthen the justification for having an intervention specifically targeted toward this demographic group.
• No theory or hypotheses are presented about why increased PA may lead to better behavioral control of asthma.
• Investigators do not provide any hypotheses for the potential moderators that they plan to assess.
• In Aim 3, how will investigators determine that reach and acceptability are adequate?

Investigator(s):
Strengths • Dr. Nyenhuis' background in implementation science is a particular strength.They have also conducted the preliminary work (as part of a K01 award) that provides important preliminary data for this proposal.
• The team has a history of working together.

Strengths
• Most previous research on PA interventions for adults with asthma has not involved a lifestyle PA approach.
• Researchers will examine maintenance effects for the lifestyle PA intervention.
• Researchers have tailored the intervention for a high-risk group: African American women.

Weaknesses
• Innovation would be strengthened by more details re: justification for tailoring an intervention specifically for this demographic group.

Strengths
• Investigators have conducted a pilot study (n=53) of a multicomponent culturally-tailored lifestyle PA intervention for African American women with asthma.This study showed that women in the intervention (vs.control group) significantly increased MVPA.Indices of feasibility and acceptability were good, and feedback from participants was used to refine the intervention.This provides a good basis for the next step in this line of research.
• Investigators provide justification for the length of the intervention phase.
• Interventions and control group are well-described.
• Rigorous aspects of the design include: data collectors who are blinded to treatment group assignment, use of self-report and objective (spirometry, accelerometry) measures of outcome, use of an intent-to-treat approach to data analysis, and a comprehensive approach to intervention fidelity assessment.

Weaknesses
• Investigators might provide a smartphone or tablet to women who don't have one so that they may participate in the study.
• Investigators should use the PHQ-9 rather than the PHQ-8 unless there is a very strong rationale.From a human subjects perspective, it is better to ask about suicide --as that gives researchers an opportunity to intervene and provide necessary referrals or resources.BMHO NYENHUIS, S • The study should be powered to detect a minimally clinically important differences that is specific to the outcome of interest (asthma control), not general.Power analyses also should not be based on effect sizes from pilot data which likely have a wide confidence interval around them.
• The qualifications or background of the health coaches who engage in goals-based text messaging is unclear.Will these be nurses?
• There is minimal discussion of the theoretical rationale for the various intervention components (e.g., group meeting format, group meeting content, text messaging, provision of Fitbit).Why is this the right combination of intervention components?

Strengths
• University of Illinois has excellent academic and clinical resources, including strong support for research.
• Investigators have a back-up plan if they are not able to recruit the required numbers from the initial sites.

Weaknesses
• There is no information provided about the University of Chicago site.This site will be responsible for recruiting participants.
• It is unclear whether there is an adequate pool of potentially eligible people from which to recruit participants.Investigators need to recruit 224 women from 8436 African American women in the right age range.If the rate of asthma is 11%, then n= 928 are expected to have asthma.It is unclear how many will also be physically inactive, not pregnant, have sub-optimally controlled asthma, and no medical contraindications.Of those who meet these inclusion criteria, how many will agree to participate?
Study Timeline:

Strengths
• Timeline is likely reasonable, but requires more detail to adequately evaluate.

Weaknesses
• Timeline should be more detailed, with start-up and recruitment milestones, divided into quarters (rather than years).

Protections for Human Subjects:
Acceptable Risks and/or Adequate Protections • Investigators detail possible risks due to physical activity, with a comprehensive plan for prevention and management.
Data and Safety Monitoring Plan (Applicable for Clinical Trials Only):

Acceptable
• Plan to use an independent safety monitor who will review all SAEs, dropouts, and AEs.• Given the possibility of SAEs (which may or may not be related to study participation) in this medically ill population, and the size of the trial, investigators and the funding agency may decide that a full DSMB is warranted.
Inclusion Plans: • Sex/Gender: Distribution justified scientifically • Race/Ethnicity: Distribution justified scientifically • Inclusion/Exclusion Based on Age: Distribution not justified scientifically • Investigators plan to include women aged 18-65.I don't see why they couldn't include older adults provided they meet inclusion criteria.If an older adult has certain physical restrictions (as mentioned in the justification), they would likely not meet inclusion criteria.
• Investigators will enroll African American women only.

Vertebrate Animals:
Not Applicable (No Vertebrate Animals)

Biohazards:
Not Applicable (No Biohazards) Resource Sharing Plans: Footnotes for 1 R01 MD017277-01; PI Name: Nyenhuis, Sharmilee Maria NIH has modified its policy regarding the receipt of resubmissions (amended applications).See Guide Notice NOT-OD-18-197 at https://grants.nih.gov/grants/guide/notice-files/NOT-OD-18-197.html.The impact/priority score is calculated after discussion of an application by averaging the overall scores (1-9) given by all voting reviewers on the committee and multiplying by 10.The criterion scores are submitted prior to the meeting by the individual reviewers assigned to an application, and are not discussed specifically at the review meeting or calculated into the overall impact score.Some applications also receive a percentile ranking.For details on the review process, see http://grants.nih.gov/grants/peer_review_process.htm#scoring.

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How will you keep individual members of the Experimental and Control groups from contaminating each other?Sex/Gender: Distribution justified scientifically • Race/Ethnicity: Distribution justified scientifically• Inclusion/Exclusion Based on Age: Distribution justified scientifically Strength of this application in include the focus on a group -African American women -who disproportionately experience negative effects of asthma.PA interventions have been shown to improve asthma control.A lifestyle PA approach is innovative in this particular context, and has been 1 The panel agreed that there was insufficient scientific justification for excluding women over the age of 65.COMMITTEE BUDGET RECOMMENDATIONS:The budget was recommended as requested.

Study Timeline: Strengths • Appropriate timeline Weaknesses • None Protections for Human Subjects:
Acceptable• I suggest including the intervention manual in this section.It would be important to share this with other teams interested in this type of research Budget and Period of Support: Collectively, the team has expertise in multi-site clinical trials, biostatistictics, behavioral interventions for asthma, interventions targeted toward African American women, assessment of PA and behavioral mechanisms, lifestyle PA interventions, mHealth, implementation science, and analysis of qualitative data.