Sickle Cell DiseasePhase 2GRACENCT04906447
Hybrid Effectiveness-Implementation Trial of Guided Relaxation and Acupuncture for Chronic Sickle Cell Disease Pain
A Phase 2 study testing Guided Relaxation and Acupuncture in people with Sickle Cell Disease, run by University of Illinois Chicago at 5 sites in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Guided Relaxation and Acupuncture
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 379 participants
- Where
- 5 sitesUnited States
- Study dates
- 24 Nov 2021to 28 Feb 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Emory University
Atlanta, Georgia, 30322
Johns Hopkins University
Baltimore, Maryland, 21218
University of Illinois at Chicago
Chicago, Illinois, 60612
Duke University
Durham, North Carolina, 22710
University of Florida
Gainesville, Florida, 32610
About this study
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.
Read more
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.
- Conditions
- Sickle Cell Disease
- Being tested
- Guided Relaxation, Acupuncture
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Guided RelaxationBehavioural
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.
AcupunctureOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Control arm | No intervention | Participants randomized to the control arm will receive usual care |
| Acupuncture | Experimental | Acupuncture treatments twice a week for five weeks Receives: Other: Acupuncture |
| Guided Relaxation | Experimental | Daily use of a guided relaxation app for 6 weeks Receives: Behavioral: Guided Relaxation |
What is being measured
The primary outcome is the main question the study is designed to answer.
PROMIS Pain Interference
Scores range from 4-20; higher scores indicate that pain is interfering with daily activities more
Measured: 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
Measured: 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
Measured: From Baseline to 24 weeks
Secondary outcomes (8)
Generalised Anxiety Disorder Questionnaire (GAD-7)
Measure of Anxiety with scores ranging from 0-21. Higher scores indicate higher levels of anxiety.
Measured: 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.
Measured: From Baseline to 24 weeks
PROMIS sleep disturbance 8a
8-40 rating with higher scores indicating greater severity of sleep disturbance
Measured: From Baseline to 24 weeks
Sleep duration
Hours a participant has slept
Measured: From Baseline to 24 weeks
Pain Catastrophizing Scale (PCS)
0-52 scale with higher scores indicating more catastrophizing thoughts are present
Measured: 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
Measured: 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
Measured: From Baseline to 24 weeks
Gastrointestinal Constipation 9a
9-45 scale with higher scores indicating more severe constipation symptoms
Measured: From Baseline to 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2021
- Study start24 Nov 2021
- Primary completion2 Jun 2025
- Study completion28 Feb 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by University of Illinois ChicagoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 379 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Illinois Chicago
- Sponsor type
- University, hospital or other
- Collaborators
- University of Florida, Duke University, National Center for Complementary and Integrative Health (NCCIH)
- Responsible party
- Principal investigator, Ardith Doorenbos, University of Illinois Chicago
- Investigators
- Ardith Doorenbos, PhD, RN, FAAN, Principal investigator, University of Illinois Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04906447
- Sponsor's protocol ID
- 2021-0124
- Other IDs
- 1UG3AT011265-01
- Acronym
- GRACE
- Status last verified
- Mar 2025
- First submitted
- 28 Apr 2021
- Last updated
- 3 Mar 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Fanfan D, Prince EJ, Molokie RE, Schlaeger JM, Shah N, Doorenbos AZ, Ezenwa MO, Matthie NS, Knisely MR, Steffen AD, Wilkie DJ, Carroll CP. Depression, pain, and catastrophizing in adults with sickle cell disease and chronic pain. Gen Hosp Psychiatry. 2026 Sep 24;103:93-100. doi: 10.1016/j.genhosppsych.2026.09.008. Online ahead of print.
PubMed 42804984Knisely 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.
PubMed 37184905Doorenbos 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.
PubMed 36852100
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hybrid Effectiveness-Implementation Trial of Guided Relaxation and Acupuncture for Chronic Sickle Cell Disease Pain
- ClinicalTrials.gov ID
- NCT04906447
- Acronym / sponsor ID
- GRACE / 2021-0124
- Conditions
- Sickle Cell Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 379 participants (actual)
- Lead sponsor
- University of Illinois ChicagoUniversity, hospital or other
- Collaborators
- University of Florida, Duke University, National Center for Complementary and Integrative Health (NCCIH)
- Study start
- 24 Nov 2021 (actual)
- Primary completion
- 2 Jun 2025 (actual)
- Study completion
- 28 Feb 2026 (actual)
- First posted
- 28 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Control arm | No intervention | –Participants randomized to the control arm will receive usual care |
| Acupuncture | Experimental | Other: AcupunctureAcupuncture treatments twice a week for five weeks |
| Guided Relaxation | Experimental | Behavioral: Guided RelaxationDaily use of a guided relaxation app for 6 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Guided RelaxationGuided 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. | Behavioural | Guided Relaxation |
| AcupunctureAcupuncture 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. | Other | Acupuncture |
Primary outcome
PROMIS Pain Interference
Time frame: From Baseline to 24 weeks
Scores range from 4-20; higher scores indicate that pain is interfering with daily activities more
Pain, Enjoyment of Life and General Activity scale (PEG)
Time frame: From Baseline to 24 weeks
0-10 rating on pain intensity, enjoyment of life and general activity
PROMIS Physical Function
Time frame: From Baseline to 24 weeks
4-20 rating on the impact of pain on ability to perform normal activities; higher scores indicate greater impact of pain on physical function
8 secondary outcomes
Generalised Anxiety Disorder Questionnaire (GAD-7)
Time frame: From Baseline to 24 weeks
Patient Health Questionnaire Depression Scale (PHQ)
Time frame: From Baseline to 24 weeks
PROMIS sleep disturbance 8a
Time frame: From Baseline to 24 weeks
Sleep duration
Time frame: From Baseline to 24 weeks
Pain Catastrophizing Scale (PCS)
Time frame: From Baseline to 24 weeks
Patient's Global Impression of Change (PGIC)
Time frame: From Baseline to 24 weeks
Tobacco, Alcohol, Prescription medication, and other Substance use (TAPS1)
Time frame: From Baseline to 24 weeks
Gastrointestinal Constipation 9a
Time frame: From Baseline to 24 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2026.
- Derived from this study: PubMed 42804984Fanfan D, Prince EJ, Molokie RE, Schlaeger JM, Shah N, Doorenbos AZ, Ezenwa MO, Matthie NS, Knisely MR, Steffen AD, Wilkie DJ, Carroll CP. Depression, pain, and catastrophizing in adults with sickle cell disease and chronic pain. Gen Hosp Psychiatry. 2026 Sep 24;103:93-100. doi: 10.1016/j.genhosppsych.2026.09.008. Online ahead of print.
- Derived from this study: PubMed 37184905Knisely 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.
- Derived from this study: PubMed 36852100Doorenbos 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.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ardith Doorenbos, PhD, RN, FAAN principal investigator
University of Illinois Chicago
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Guided Relaxation and Acupuncture in people with Sickle Cell Disease, run by University of Illinois Chicago at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PROMIS Pain Interference (time frame: From Baseline to 24 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04906447, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Mar 2026.