Planning the “Activity and Nutrition Trial in Lupus to

Energize and Renew” (ANTLER Study)

Linda Ehrlich-Jones, PhD, RN March 26, 2015

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Disclosures

Funding from: NIH-NIAMS U34-AR064513 NIH-NIAMS R21-AR059989 NIH-NIAMS T32-AR007611 Northwestern University Dean’s Office Seed

Grant

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Objectives

1) Describe the planning process for a clinical trial.

2) Discuss lessons learned through pilot testing an intervention.

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Introduction Systemic Lupus Erythematosus (SLE) is a

chronic, systemic, autoimmune disease characterized by pronounced inflammation that affects up to 1.5 million persons in the US.

More common in: – Women (9:1) – African-American, Hispanic, and Asian

populations

ACR Image Bank

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Introduction Most organ systems can be involved. While excess mortality has decreased, a major

ongoing cause of morbidity is chronic, debilitating fatigue.

Fatigue leads to decrease in quality of life, increase risk of work disability, and associated health care costs.

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Introduction An unmet need in the management of patients

with SLE is identification of effective strategies to decrease fatigue.

Physical activity and dietary intake are modifiable behaviors considered potentially relevant to reducing fatigue in patients with SLE.

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Activity in Lupus to Energize and Renew (ALTER)

R21: cross-sectional study of 129 adults with SLE

Primary outcome was Fatigue measured by the Fatigue Severity Scale (FSS)

Secondary outcome included physical activity measured by tri-axial accelerometers worn for 7 days

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ALTER Fatigue

0

1

2

3

4

5

6

7Fatigue Severity Scale

≥ 4 clinically significant

level of fatigue

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ALTER Participants and Public Health Physical Activities Guidelines (n=129)

Inactive, 44%

Low active, 43%

Active , 13%

Very active, 4%

SLE patients are sedentary

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ANTLER Pilot 1 6-week behavioral intervention consisting of individual

tailored coaching and three group educational sessions to promote physical activity and increased consumption of fruits and vegetables in persons with SLE

Motivational interviewing used in coaching sessions that led to goal setting for physical activity and diet changes

8 participants started and 7 completed 6 Women and 2 Men 4 AA, 2 Asian, 2 Caucasian

Measuring Physical Activity

Participants wore triaxial accelerometer at natural waistline during waking hours for 7 days.

They kept a log as to when they put on and took off.

Accelerometer Data Uniaxial

Triaxial

z axis

Vector Magnitude

x axis

y axis

y axis

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Measuring Diet

ASA24™ Announcements

• Dietary Assessment Primer

• ASA24-Canada-2014 was released! Quick Links

• Respondent Web Site Demonstration (ASA24-2014 and ASA24-Kids-2014)

• Respondent Web Site Demonstration (ASA24-2011 and ASA24-Kids-2012)

• Researcher Web Site

• Join the ASA24 Listserv

ASA24 is a freely available Web-based tool that enables automated self-administered 24-hour recalls. ASA24 consists of a Respondent Web site used to collect recall data and a Researcher Web site used to manage study logistics and obtain data analyses. Two US Respondent Web sites (English and Spanish) are currently available for registering new studies: ASA24-2014 (for adults) and ASA24-Kids-2014. One Canadian version, ASA24-Canada-2014 (English only) is currently available for administration and the ability to obtain analyses for this will be available soon. Still available until March of 2015 are two previous versions of the Respondent Web site:ASA24-2011 (for adults) and ASA24-Kids-2012. Further information on the Respondent and Researcher Web sites is provided in the sections below.

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Lesson Learned From ANTLER Pilot 1 Intervention well received

– Individual sessions: liked 1-on-1 and goal setting – Group sessions: felt they learned a lot from other participants,

wanted more time to interact with other participants, wanted website portal to continue interaction outside of group

Assessments completed online on Assessment Center and ASA-24 – Assessment Center worked well to measure all PRO’s – ASA-24 too labor intensive

Missed data capture

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Planning for the Clinical Trial NIAMS U34 Planning Cooperative Agreement for investigator-

initiated clinical interventional trials Designed to permit the necessary planning, design, and

preparation of documentation prior to investigator-initiated clinical trials.

Completion of U34 planning grant milestones is recommended prior to submission of a clinical trial through a U01 mechanism.

Trials must be hypothesis-driven, milestone-defined, related to the research mission of the NIAMS and considered high priority by the Institute.

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Other Institutes currently offering U34 NIDDK NIDCD

New mechanism: R34

– NIAID – NIDCR – NIA

1) Develop protocol for U01 application 2) Revise behavioral interventions from IMPAACT, JointADventure, and ANTLER pilot 3) Develop protocol for control arm (focus on education not behavior change) 4) Submit U01 application for ANTLER 5) Develop manual of operations (MOP), forms and data systems, smartphone application, training and educational materials 6) Prepare Human Subjects Protection Documents and Develop Data Safety Monitoring Plan

U34 Specific Aims:

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Innovation Emphasis on increasing physical activity in conjunction with

modifying dietary intake using an intensive motivational interviewing (MI) behavioral intervention strategy

Use of state-of-the-art approaches to assess physical activity and patient reported outcomes (PROs) in patients with SLE

Assessment of dietary intake to evaluate both nutrient content and energy density which may offer new insights regarding potential contributors to fatigue in this population

Use of state-of-the-art technology for communication strategies and self-monitoring of behavior change in patients with SLE

ANTLER Research Team Organization Chart

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Half Day Retreat Brainstorming with entire U34 team Felt the need to perform ANTLER Pilot 2 to

test – smartphone application and coaching

interface, – wearing of accelerometer 24 hours per day

for 7 days to assess sleep, – Nutrition Data System for Research (NDSR)

diet interview

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ANTLER Pilot 2 6-week intervention using Fitbit and ANTLER

Smartphone apps and coaching interface – Self-monitoring physical activity, fruit/vegetable

consumption, sleep quantity and quality Motivational Interviewing with goal setting 6 participants: 5 Women, 1 Man 4 AA, 1 Hispanic, 1 Caucasian 3+ participated in ANTLER Pilot 1

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ANTLER Pilot 2 Motivational Interviewing

– Arthritis Comprehensive Treatment Assessment adapted for SLE

– Coaching per phone and/or email Smartphone app and coaching interface Fitbit

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Antler Pilot 2: Demographics

N %Race

Caucasian 1 16.67African American 4 66.67

Hispanic 1 16.67

N %Sex

Female 5 83.33

N %Marital Status

Single 1 16.67Married 3 50

Divorced 2 33.33

N %Weight Status

Normal Weight: <25 1 16.67Over Weight: >=25 or <30 2 33.33

Obese: >=30 3 50

N Mean Std Dev Minimum Median MaximumAge at time of visit 6 51.66 13.02 31.49 52.39 71.12

Disease Duration 6 13.48 7.62 2.92 18.16 18.83WEIGHT 6 191.05 47.72 135.5 180.8 251HEIGHT 6 66.53 2.91 64.27 65.95 72.1

BMI 6 30.15 6.35 23.04 29.52 39.9BP Diastolic 6 78.83 12.35 61 80 94BP Systolic 6 123.5 8.22 113 123 137Waist (cm) 6 100.75 13.48 87 99.75 118.5

Hip (cm) 6 110.25 10.9 95.5 109.5 125Waist/Hip Ratio 6 0.91 0.08 0.84 0.9 1.06

Years of Education Completed 6 14.67 2.16 12 15.5 17

BASELINE PATIENT CHARACTERISTICS

ANTLER Smartphone App and Fitbit

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Coaching Interface

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Daily Steps (Fitbit)

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Very Active Minutes (Fitbit)

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Accelerometry Data

Subject

Average Vector

Magnitude Baseline

Average Vector

Magnitude 6 wk Difference

2 377387 280984 -964034 917080 996982 79901.85 411287 319641 -916467 586171 296459 -28971110 410956 . .11 722006 576733 -145273

Subject

Average Light

Activity Baseline

Average Light

Activity 6 wk Difference

2 385 316.25 -68.754 430 370.14 -59.865 258.86 208 -50.867 425.57 255 -170.5710 364.29 . .11 386.14 382.38 -3.77

Subject

Average Mod/Vig Activity Baseline

Average Mod/Vig Activity

6 wk Difference2 13.14 7.38 -5.774 93.57 110.71 17.145 42.57 30.63 -11.957 50 14.5 -35.510 18.57 . .11 78.86 46.88 -31.98

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ANTLER Pilot 2 NDSR

(n=6) Mean Std Dev Median Mean Std Dev Median

2231.66 1389.17 1848.52 Total Energy (kcal) 1647.43 1222.99 1207.0287.96 51.57 89.69 Total Fat (g) 48.4 24 43.4834.26 9.61 33.08 % Calories From Fat 30.89 12.64 30.81

268.07 187.51 219.22 Total Carb (g) 203.48 136.79 160.746.25 11.09 46.49 % Calories From Carbohydrate 47.95 7.01 47.4388.48 32.45 76.66 Total Protein (g) 79.41 76.88 58.82

18.2 6.95 18.11 % Calories From Protein 18.31 7.49 15.158.69 18.82 58.1 Animal Protein (g) 58.99 66.23 37.9829.79 17.49 28.78 Vegetable Protein (g) 20.42 12.07 16.28

9.4 22.97 0 Alcohol (g) 15.45 37.75 0.021.34 3.26 0 % Calories From Alcohol 2.8 6.79 0.03

26.84 18.05 22.43 Total SFA (g) 18.89 11.28 16.2410.22 2.31 9.86 % Calories From SFA 12.43 7.85 11.7234.32 20.07 35.68 Total MUFA (g) 16.26 8.66 14.6113.74 6.4 12.71 % Calories From MUFA 9.82 2.75 10.5120.19 12.53 18.96 Total PUFA (g) 8.78 3.85 8.95

7.81 2.52 6.93 % Calories From PUFA 5.85 2.98 5.2619.67 12.44 21.63 Total Dietary Fiber (g) 18.65 8.81 16.18

920.58 561.61 890.1 Calcium (mg) 607.66 258.37 519.85430.65 261.27 382.34 Magnesium (mg) 315.02 238.3 245.63

2670.36 2265.16 1693 Sodium (mg) 1866.46 1626.12 1386.032597.96 1131.07 2616.72 Potassium (mg) 2127.72 1861.45 1402.45

1.59 1.38 0.92 Omega-3 Fatty Acids (g) 0.91 0.73 0.53100.19 102.84 73.71 Added Sugars (by available carb) (g) 56.12 50.36 55.81248.03 187.24 203.41 Available Carbohydrate 184.63 131.6 149.25

94.44 95.57 70.06 Added Sugars (by total sugars) (g) 45.63 45.84 28.37

BASELINE NUTRIENT FOLLOW-UP

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Lessons Learned from ANTLER Pilot 2 Fitbit app and ANTLER app confusion Not all Smartphones were compatible Charging Fitbit-need computer or external charger Loss of Fitbit Fitbit/Actigraph sleep issues Other self-monitoring goals: water, calories

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Preliminary Specific Aims for U01

Test the effectiveness of the ANTLER intervention for SLE to decrease fatigue, the primary outcome.

Test the effectiveness of the ANTLER intervention for SLE to improve PA and diet behavior, the secondary outcomes.

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Original Preliminary Trial Design 12 month active arm (intervention)

– Baseline individual counseling session – 3 months of biweekly intensive lifestyle group counseling and 6

months of monthly lifestyle group counseling – 4 additional individual counseling sessions at 6 weeks, 3

months, 6 months, and 11 months. 12 month comparator arm (control)

– Details TBD but focus is on education, will include individual and group sessions

– But will NOT include healthy lifestyle counseling or motivational interviewing

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Proposed Study Designs- 6 month intervention, continue self-monitoring, and 6

month follow up Experimental vs Standard of Care

– Experimental: Group sessions, individual sessions, self-monitoring

– Standard of Care: Education on living with SLE Factorial Design:

– Group only; Group and individual sessions; Group and self-monitoring; Group, individual sessions and self-monitoring

Step-Up Approach: – Group; add individual sessions; add self-monitoring

Concept Variable Measure Data Collection

Background Variables

Demographics

Age, gender, race, marital status, education Level

Chicago Lupus Database protocol

Online questionnaire via Assessment Center

Current Health Disease activity, damage

*SLEDAI, ACR/SLICC-DI

Face to face interview, MD history and examination

Disease duration, medications, co-morbid conditions including fibromyalgia, anemia, hypothyroidism

Chicago Lupus Database protocol

Face to face interview, MD history, examination (fibromyalgia)

*SLEDAI= Systemic Lupus Erythematosus Disease Activity Index; SLICC/ACR-DI= Systemic Lupus International Collaborating Clinics/American College of Rheumatology-Damage Index

Data Collection for ANTLER [Guided by Cox’s Interaction Model of Client Health Behavior]

Concept Variable Measure Data Collection Mediating Variables

Motivation Motivation Motives for Physical Activity Measure-Revised (MPAM-R); Food Choice Questionnaire (FCQ)

Self-report: Online questionnaires via Assessment Center

Health Behaviors

Physical Activity Physical activity Accelerometer counts/day; Minutes of non-sedentary activity/day; Minutes of moderate-vigorous physical activity/day ; International Physical Activity Questionnaire (IPAQ)

Actigraph accelerometry (sleep) Online questionnaire via Assessment Center

Diet Behavior 24 hour dietary recall NDSR not ASA24 Self-report: Online questionnaire

Data Collection for ANTLER

Concept Variable Measure Data Collection Health Outcomes

Physical Function Physical Function Timed 20 meter walk test In-person clinical assessment

Blood pressure and anthropometric measurements

BP, height, weight, waist-hip ratio

*MESA Protocol In person clinical assessment

Patient-reported outcomes

Fatigue Fatigue Severity Score (FSS); PROMIS-Short Form

Self-report: Online questionnaire via Assessment Center

Pain PROMIS-Short Form Self-report: Online questionnaire via Assessment Center

Depression PROMIS-Short Form Self-report: Online questionnaire via Assessment Center

Anxiety PROMIS-Short Form Self-report: Online questionnaire via Assessment Center

Sleep Disturbance PROMIS-Short Form Self-report: Online questionnaire via Assessment Center

Sleep-Related Impairment

PROMIS-Short Form Self-report: Online questionnaire via Assessment Center

Physical Function PROMIS-Short Form Self-report: Online questionnaire via Assessment Center

*MESA= Multi-Ethnic Study of Atherosclerosis

Data collection for ANTLER

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Outcomes Less Fatigue—FSS (primary) Improved QoL– PROs, e.g. PROMIS pain, fatigue, anxiety,

depression, sleep disturbance and interference – Measure sleep, actigraph, other tools? – PROMIS-short forms or CATS

Less Sedentary – physical activity--accelerometer (objective) and IPAQ (subjective) – physical function--gait speed (objective) and PF from PROMIS

(subjective) Improved Nutrition—NDSR- what change is significant? Other?? -bio-specimens for mechanistic studies; health utility

and work status

Acknowledgements: Study Participants

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Cores Members Goals Leadership core Rosalind Ramsey-

Goldman and Linda Ehrlich-Jones

Oversee planning activities; prepare U01 application

Methodology/Data Management Core

Joan Chmiel and Rowland Chang; Anh Chung, Irene Helenowski, Dan Erickson, Madeleine Ma

Oversee study design, power, data analysis, data management, data security

Patient Reported Outcomes (PROs)

Susan Yount, Mary Mahieu; Anh Chung, Dan Erickson

Expertise in PROs; support for assessment center

Research Support Karen Mancera-Cuevas: Patricia Murphy, Danielle Lerner, Liliana Medina

Manage day to day operations of trial; regulatory; recruitment; training of staff; group activities

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Cores Members Goals Physical Activity Measurement and Development

Dorothy Dunlop and Pamela Semanik; Jing Song

Oversee physical activity assessments objective and subjective; manage data and input on intervention and interpretation of data

Nutrition Measurement and Intervention Development

Linda Van Horn; Eileen Vincent, Liliana Medina, Mary Mahieu

Oversee selection and data collection of diet quality and quantity; input on intervention; biomarkers

Behavior Assessment and Intervention Development

Bonnie Spring and Christine Pellegrini; Gleb Iakovlev, Miriam Davidson

Develop behavioral treatment and control education arms; Motivational interviewing training; oversee technology tools

New areas: sleep assessment/light exposure/depression

Phyllis Zee, Kathy Reid, and Kathy Wisner

Incorporate objective sleep assessments, light intervention; coordinate with PRO data

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Thank You

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Group Sessions

Experimental monthly group sessions (10 people per group): – 1: Intro to program and technology – 2: physical activity/safety – 3: fruit/vegetable volumetrics – 4: sleep/fatigue – 5: motivation – 6: eating outside the home

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Group Sessions Standard of Care monthly group sessions (10 people per

group): – 1: Intro to program and technology in a group – 2: How do I know if I have SLE? – 3: How do I know if what I feel is SLE? – 4: What should I tell my other doctors about my SLE? – 5: What community resources are there for people with SLE? – 6. What do I need to know to live with SLE?

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Individual Sessions Experimental Group

Check in with coach regarding technology 2-3 days after group session on technology

Initial coaching session 1 week later for ACTA and goal setting 1st month every other week call with coach Individual sessions by text, email or phone thereafter

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Individual Sessions Standard of Care Group

Check in with coach regarding technology 2-3 days after group session on technology

Bi-weekly text messages regarding self-management

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Self-monitoring Standard of Care Group Self-monitoring of SLE symptoms Smartphone app from Lupus Initiative

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Self-monitoring Experimental Group Self-monitoring of physical activity, consumption of fruits

and vegetables, sleep/fatigue Smartphone app(s) Fitbit and ANTLER

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Preliminary Studies and Retreat Action Items

ALTER study-reviewed at retreat 7/2/14 – physical activity assessment and patient reported outcomes

ANTLER pilot I-reviewed at retreat 7/2/14 – short term intervention feasibility study with group and

individual coaching sessions ANTLER pilot II-action item from retreat 7/2/14

– Short term intervention to test feasibility of self monitoring – Test another dietary assessment tool

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Summary from ALTER

Self-reported International Physical Activity Questionnaire (IPAQ) showed modest associations with accelerometer measures in adults with SLE (Ahn GE et al Arthritis Care Res (Hoboken). 2014 Sep 23. doi: 10.1002/acr.22480. [Epub ahead of print])

Self-reported IPAQ and objective accelerometer data may be useful for

different purposes in future research studies – IPAQ provides descriptive data on the types of PA performed – Accelerometer data may be useful when a change in PA is the

outcome of interest in intervention studies (same as above)

Modest negative correlations were seen between fatigue, pain, and physical activity – First report of PROMIS data results and internal consistency of domains in

adult SLE (Mahieu M et al, submitted for Arthritis Care & Res (Hoboken) for themed issue on fatigue in rheumatic diseases)

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Rationale for Study Fatigue is most disabling and enduring complaint among

patients with SLE along disease continuum Fatigue is a major problem for SLE patients and it is not

consistently associated with disease activity, disease damage, or medications

To date there are limited treatment options for fatigue Physical activity and dietary intake are modifiable

behaviors considered potentially relevant to reducing fatigue in patients with SLE

We propose to design an intensive lifestyle behavior counseling program modeled after Diabetes Prevention Program (DPP) to reduce fatigue in patients with SLE

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Site Quality Management Plan

Training – Active intervention (includes motivational interviewing) – Control intervention (education; no behavioral or lifestyle

content) Treatment fidelity Data management and security

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Timing of Assessments 4 assessment times:

– T0: Baseline – T1: 3 months post randomization – T2: 6 months post randomization – T3: 12 months post randomization