Hybrid Effectiveness-Implementation Trial of Guided Relaxation and Acupuncture for Chronic Sickle Cell Disease Pain (GRACE)

The investigators will conduct a hybrid type 1 effectiveness implementation trial to assess the effectiveness of acupuncture and guided relaxation on 360 people with Sickle Cell Disease (SCD), while observing and gathering information on implementation in three health systems: University of Illinois Hospital & Health Sciences System, University of Florida Health, and Duke University Health Systems. Each serves a large population with SCD, uses EPIC as their electronic health record, and has a Clinical and Translational Science Award (CTSA), which will help speed the translation of discovery into improved patient care. During the UH3 Implementation Phase, the 3-arm, 3-site randomized controlled trial will follow a quantitative modified SMART design, a pragmatic trial that evaluates adaptive interventions where the guided relaxation and acupuncture interventions respond to patients' characteristics and evolving pain status. The investigators rely on the Consolidated Framework for Implementation Research (CFIR) to plan, execute, and evaluate associated implementation processes. The use of complementary and integrative health (CIH) therapies by those with SCD to reduce pain and opioid use, to help enable them to better cope with their pain, is well known, but there are few studies that evaluate the effectiveness of these therapies, and none that also evaluates the implementation across multiple health care systems and patient populations as this study will.

Aim 1: Determine the effectiveness of guided relaxation and acupuncture as compared to usual care in decreasing pain and opioid use for SCD patients. Hypothesis: At 6-weeks, SCD patients randomized to either CIH intervention will have a greater decrease in pain, opioid use, sleep, anxiety, depressive symptoms, and pain catastrophizing compared to SCD patients randomized to usual care.

Aim 2: Identify the best adaptive intervention for improved outcomes by documenting outcomes among adaptive intervention sequences: (1) initiate guided relaxation and switch to acupuncture for non-responders at midpoint; (2) initiate guided relaxation and continue with guided relaxation for non-responders at midpoint; (3) initiate acupuncture and switch to guided relaxation for non-responders at midpoint or (4) initiate acupuncture and continue with acupuncture for non-responders at midpoint.

Aim 3: Explore differences in response to the adaptive interventions by age and sex.

Aim 4: Identify implementation facilitators, challenges, and solutions for structures and processes that contribute to the seamless integration of CIH therapies into the 3 health systems by conducting individual interviews with participants in the intervention group who responded to the intervention and those who did not. The investigators will also conduct focus groups with hospital personnel at 4 timepoints.

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Other: Acupuncture; Behavioral: Guided Relaxation

• Study Type: Interventional
• Enrollment (Actual): 379
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago
  • Maryland
    • Baltimore, Maryland, United States, 21218
      • Johns Hopkins University
  • North Carolina
    • Durham, North Carolina, United States, 22710
      • Duke University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Diagnosis of sickle cell disease based on hemoglobin electrophoresis
• Provision of signed and dated informed consent form
• Able to speak and understand English
• Chronic pain, defined as a response of "Some days," "Most days" or "Every day" to the question, "In the past 3 months, how often have you had pain?" (Answer options: Never, Some days, Most days, Every day)
• Current pain interference using the general activity question from PEG, score ≥3 on 0-10 scale

Exclusion Criteria:

• Has had a stem cell transplant for sickle cell disease
• Current incarceration
• Any other condition that the investigator considers precludes participation in the clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control arm; Participants randomized to the control arm will receive usual care
Experimental: Acupuncture; Acupuncture treatments twice a week for five weeks	Other: Acupuncture; Acupuncture is a body-based therapy that includes the insertion of thin needles at strategic points on the body that has been proven effective for reducing pain.
Experimental: Guided Relaxation; Daily use of a guided relaxation app for 6 weeks	Behavioral: Guided Relaxation; Guided relaxation uses the mind to reduce pain, promote well-being, and improve physical function. Guided relaxation is a state of concentration and focused attention that gives people more control over their pain experience and its impact and an increased sense of well-being.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PROMIS Pain Interference	Scores range from 4-20; higher scores indicate that pain is interfering with daily activities more	From Baseline to 24 weeks
Pain, Enjoyment of Life and General Activity scale (PEG)	0-10 rating on pain intensity, enjoyment of life and general activity	From Baseline to 24 weeks
PROMIS Physical Function	4-20 rating on the impact of pain on ability to perform normal activities; higher scores indicate greater impact of pain on physical function	From Baseline to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Generalised Anxiety Disorder Questionnaire (GAD-7)	Measure of Anxiety with scores ranging from 0-21. Higher scores indicate higher levels of anxiety.	From Baseline to 24 weeks
Patient Health Questionnaire Depression Scale (PHQ)	0-24 rating of depression. 10 or greater total is considered major depression, 20 or more is severe major depression.	From Baseline to 24 weeks
PROMIS sleep disturbance 8a	8-40 rating with higher scores indicating greater severity of sleep disturbance	From Baseline to 24 weeks
Sleep duration	Hours a participant has slept	From Baseline to 24 weeks
Pain Catastrophizing Scale (PCS)	0-52 scale with higher scores indicating more catastrophizing thoughts are present	From Baseline to 24 weeks
Patient's Global Impression of Change (PGIC)	1-7 scale with higher scores indicating more improvement in pain from the patient's perspective	From Baseline to 24 weeks
Tobacco, Alcohol, Prescription medication, and other Substance use (TAPS1)	1-20 scale with higher score relating to more frequent substance use over the past 12 months	From Baseline to 24 weeks
Gastrointestinal Constipation 9a	9-45 scale with higher scores indicating more severe constipation symptoms	From Baseline to 24 weeks

Collaborators and Investigators

• Sponsor: University of Illinois at Chicago
• Collaborators: Duke University; University of Florida; National Center for Complementary and Integrative Health (NCCIH)
• Investigators: Principal Investigator: Ardith Doorenbos, PhD, RN, FAAN, University of Illinois at Chicago

Publications and helpful links

General Publications

• Knisely MR, Rivera E, deMartelly VA, Abdulkadir A, Doorenbos AZ, Ezenwa MO, Molokie RE, Li H, Shah N, Schlaeger JM, Patil CL. Developing an Implementation Blueprint for the NIH HEAL Initiative GRACE Trial: Perspectives on Acupuncture and Guided Relaxation for Chronic Sickle Cell Disease Pain. J Integr Complement Med. 2023 Oct;29(10):683-688. doi: 10.1089/jicm.2022.0781. Epub 2023 May 15.
• Doorenbos AZ, Schlaeger JM, deMartelly VA, Burke LA, Boyd AD, Knisely MR, Leigh JW, Li H, Mandernach MW, Molokie RE, Patil CL, Steffen AD, Shah N, Ezenwa MO. Hybrid effectiveness-implementation trial of guided relaxation and acupuncture for chronic sickle cell disease pain (GRACE): A protocol. Contemp Clin Trials Commun. 2023 Jan 18;32:101076. doi: 10.1016/j.conctc.2023.101076. eCollection 2023 Apr.

Study record dates

Study Major Dates

• Study Start (Actual): November 24, 2021
• Primary Completion (Actual): June 2, 2025
• Study Completion (Actual): February 28, 2026

Study Registration Dates

• First Submitted: April 28, 2021
• First Submitted That Met QC Criteria: May 24, 2021
• First Posted (Actual): May 28, 2021

Study Record Updates

• Last Update Posted (Actual): March 3, 2026
• Last Update Submitted That Met QC Criteria: February 27, 2026
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Anemia, Sickle Cell; Therapeutics; Complementary Therapies; Acupuncture Therapy
• Other Study ID Numbers: 2021-0124; 1UG3AT011265-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We will publish our results in open-source manuscripts that will be available to the public. Electronic copies of publications will be deposited in PubMed Central with proper tagging of metadata to ensure online discoverability and accessibility within four weeks of acceptance by a journal. To the extent feasible, Underlying Primary Data will be shared simultaneously with the publication and made immediately accessible through release under the Creative Commons Attribution 4.0 Generic License or an equivalent license, or otherwise dedicated to the public domain. Before submitting Underlying Primary Data, we will work with our Institutional Review Board (IRB) and Data Safety and Monitoring Board to assess the informed consent materials and to determine whether the Underlying Primary Data may be shared as contemplated in this policy.
• IPD Sharing Time Frame: Data will be shared within one year of the completion of the study.
• IPD Sharing Access Criteria: The data and associated documentation will be made available to users only under a data-sharing agreement that provides for (a) a commitment to using the data only for research purposes and not to identify any individual patient; (b) a commitment to securing the data using appropriate computer technology; and (c) a commitment to destroying or returning the data after analyses are completed. Such a data-use agreement will be executed through the PIs and the University of Illinois at Chicago College of Nursing. The database can then be accessed via our secure website, in a format that can be used by a variety of statistical software packages. We will make our data and results publicly available (predominately online), so that they can easily be found.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No