Integrative Medicine in Pain Management in Sickle Cell Disease
Integrative Medicine in Pain Management in Sickle Cell Disease: Assessing the Clinical Efficacy and Neurobiological Impact With Acupuncture
Study Overview
Status
Status
Conditions
Conditions
Intervention / Treatment
Intervention / Treatment
Detailed Description
Study Type
Study Type
Enrollment (Estimated)
Enrollment
Phase
Phase
- Not Applicable
Contacts and Locations
Study Contact
Study Contact
- Name: Ying Wang, MD, PhD
- Phone Number: 317-278-5045
- Email: ywa12@iu.edu
Study Contact Backup
- Name: Ying Wang, MD, PhD
- Phone Number: 317-406-5047
- Email: ywanglab@iupui.edu
Study Locations
-
-
Indiana
-
Indianapolis, Indiana, United States, 46075
- Indiana University School of Medicine
-
-
Participation Criteria
Eligibility Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Any gender
- 14-17 (Adolescents) and 18-80 (Adults) years old
- Right-handed
- Either outpatient or inpatient or status changing between each other
- Have been diagnosed with SCD (includes but not limited to SS, SC or other type) and experiencing chronic pain in the past 6 months or vaso-occlusive crisis (VOC) in the past 12 months.
- Analgesic therapy prescribed by primary hematologists (or physicians for emergency or primary care) including pain-relieving medications (e.g. Morphine, coderin, Fentanyl, Oxycodone), Hydroxyurea (e.g. Droxia, Hydrea, Siklos), L-glutamine oral powder (Endari), Crizanlizumab (Adakveo), Voxelotor (Oxbryta), and/or other palliative treatment allowed, not required.
- Willing to limit the current and the introduction of any new medications or treatment modalities for control of pain symptoms during the study visits.
- Able to travel to the study site for participating scheduled visits (questionnaires, QST, EEG and MRI) and receive acupuncture treatments up to two times weekly for 5 weeks as scheduled.
- We will recruit without regard to ethnicity, however, due to the genetic nature of SCD, subjects will primarily be African-American or of African descent, although there are individuals with SCD who come from Hispanic, southern European, Middle Eastern, or Asian Indian backgrounds. The ethnic distribution in our prior studies is 95% Black/African American with 5% Hispanic or Latino (of any race). As these are minority groups many individuals may be from lower income situations.
- Fluent in English and capable of giving written informed consent.
Exclusion Criteria:
- Subjects with Covid-19 suspicion or confirmation
- Recent/ongoing alternative pain management with acupuncture or acupuncture-related techniques within the last 6-months.
- Presence of a known coagulation abnormality: Thrombocytopenia (mild thrombocytopenia with a platelets range of 51,000-100,000/ul will be further evaluated for inclusion consideration), or bleeding diathesis that may preclude the safe use of acupuncture.
- Presence of a concurrent autoimmune or inflammatory disease such as rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, etc. that causes pain or any other chronic pain condition with pain greater than sickle pain.
Diseases/conditions history includes but not limited to:
- head injury with substantial loss of consciousness
- peripheral neuropathy of known cause that interferes with activities of daily living
- known non-SCD related Severe psychiatric illnesses (e.g. current schizophrenia, major depression with suicidal ideation).
- significant visual, motor, or auditory impairment that would interfere with ability to perform study visits-related activities
- Medication:
Recent (30 days) initiation or dose adjustment of stimulant medications, such as those used to treat ADD/ADHD (e.g., amphetamine/dextroamphetamine [Adderall®], methylphenidate, dextroamphetamine), or the fatigue associated with sleep apnea or shift work (e.g., modafinil).
- Contraindications to MRI scans includes but are not limited to: surgical clips, surgical staples, metal implants, cardiac rhythmic disorders, seizure disorders, and certain metallic dental material will not be scheduled for MRI visits.
- History vascular surgery in lower limbs or current lower limb vascular dysfunction will not receive conditioned pressure pain stimuli in the lower limb.
- Subjects with Worker's Compensation, Workman's Compensation, civil litigation or disability claims pertinent to the subject's sickle disease; current involvement in out-of-court settlements for claims pertinent to the subject's sickle disease; or currently receiving monetary compensation as a result of any of the above.
- Participation of other studies: Concurrent participation in other therapeutic trials with overlapping research purposes.
- Pregnant or nursing.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Number of Arms
Arms and Interventions
Participant Group / ArmParticipant Group / Arm |
Intervention / TreatmentIntervention / Treatment |
|---|---|
|
Experimental: Needling Acupuncture - 5 weeks
Needling acupuncture treatment will last 30 minutes per session and will be administered two times per week for 5 weeks.
Each subject will receive one course of treatment which contains 10 treatment sessions.
|
Acupuncture treatment will both main and supplementary acupoints.
Main points include GB30; ST36; LI11- LI4, GB34-SP6; LR3, SP10, DU24, DU20, Yin Tang, Ear Shen Men which are chosen based on the unique clinical features of sickle pain.
The remaining individualized acupoints will be selected and manipulated with manual acupuncture with appropriate needling techniques based on the individual "Syndrome" ("reinforce" or "reduce" or "Non reinforce or reduce") that is determined by TCM diagnosis.
|
|
Experimental: Laser Acupuncture - 5 weeks
Laser acupuncture treatment will also last 30 minutes per session and will be administered two times per week for 5 weeks.
Each subject will receive one course of laser acupuncture treatment which contains 10 treatment sessions.
|
Laser acupuncture device VitaLaser 650 (Lhasa OMS, Weymouth, MA or similar) will be positioned 1-2cm over all of the same acupoints used in verum acupuncture treatment above.
No palpation is administered prior to positioning the device and there is no physical contact between device and skin.
|
|
Experimental: Needling Acupuncture - 12 weeks
Needling acupuncture treatment will last 30 minutes per session and will be administered once per week for 12 weeks.
Each subject will receive one course of treatment which contains 12 treatment sessions.
|
Acupuncture treatment will both main and supplementary acupoints.
Main points include GB30; ST36; LI11- LI4, GB34-SP6; LR3, SP10, DU24, DU20, Yin Tang, Ear Shen Men which are chosen based on the unique clinical features of sickle pain.
The remaining individualized acupoints will be selected and manipulated with manual acupuncture with appropriate needling techniques based on the individual "Syndrome" ("reinforce" or "reduce" or "Non reinforce or reduce") that is determined by TCM diagnosis.
|
|
Experimental: Laser Acupuncture - 12 weeks
Laser acupuncture treatment will also last 30 minutes per session and will be administered once per week for 12 weeks.
Each subject will receive one course of laser acupuncture treatment which contains 12 treatment sessions.
|
Laser acupuncture device VitaLaser 650 (Lhasa OMS, Weymouth, MA or similar) will be positioned 1-2cm over all of the same acupoints used in verum acupuncture treatment above.
No palpation is administered prior to positioning the device and there is no physical contact between device and skin.
|
What is the study measuring?
Primary Outcome Measures
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Functional brain connectivity characteristics
Time Frame: changes brain connectivity features from baseline to post-treatment time point (approximately 5 weeks interval)
|
Characteristics of functional brain activity will be studied using fMRI.
|
changes brain connectivity features from baseline to post-treatment time point (approximately 5 weeks interval)
|
|
Somatosensory function
Time Frame: changes of quantitative sensory testing scores from baseline to post-treatment time point (approximately 5 weeks interval)
|
Somatosensory functionality will be examined using a board tests of which is a reliable and reproducible approach in pain research.
|
changes of quantitative sensory testing scores from baseline to post-treatment time point (approximately 5 weeks interval)
|
Secondary Outcome Measures
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Brain metabolites characteristics
Time Frame: changes of brain metabolites levels from baseline to post-treatment time point (approximately 5 weeks interval)
|
Characteristics of brain metabolites will be studied using 1H-MRS.
|
changes of brain metabolites levels from baseline to post-treatment time point (approximately 5 weeks interval)
|
|
painDETECT Questionnaire
Time Frame: changes of painDETECT scores from baseline to post-treatment time point (approximately 5 weeks interval)
|
This is 4-component questionnaires that address the location, intensity, quality of pain symptoms.
painDETECT is a nine-item questionnaire that consists of seven sensory symptom items for pain that are graded from 0= never to 5= strongly, one temporal item on pain-course pattern graded -1 to +1, and one spatial item on pain radiation graded 0 for no radiation or +2 for radiating pain.
|
changes of painDETECT scores from baseline to post-treatment time point (approximately 5 weeks interval)
|
|
Brief Pain Inventory (BPI) Questionnaire
Time Frame: changes of BPI scores from baseline to post-treatment time point (approximately 5 weeks interval)
|
A simplified BPI is used to assess the severity of pain, interference of pain on daily function, location of pain, pain medications and amount of pain relief using the rating from 0= no pain/relief/interference to 10= worst pain imaginable/complete relief/completely interferes in the past 24 hours or the past week.
|
changes of BPI scores from baseline to post-treatment time point (approximately 5 weeks interval)
|
|
Nociplastic Pain Questionnaire
Time Frame: changes of nociplastic scores from baseline to post-treatment time point (approximately 5 weeks interval)
|
A customized questionnaire that is used to examine the locations (Yes/No) and severity of the pain interference (no problem-slight-moderate--severe) for understanding the level of nociplastic pain in the past 7 days.
Widespread Pain Index and Symptom Severity will be scored from 0 to 10. Higher score connotes higher severity of nociplastic pain.
|
changes of nociplastic scores from baseline to post-treatment time point (approximately 5 weeks interval)
|
|
Hospital Anxiety and Depression Scale (HADS) Questionnaire
Time Frame: changes of HADS scores from baseline to post-treatment time point (approximately 5 weeks interval)
|
HADS is used to determine the levels of anxiety and depression that a person is experiencing in the past one week.
The HADS is a fourteen-item scale that generates: Seven of the items relate to anxiety and seven relate to depression.
Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 and 21 for either anxiety or depression.
|
changes of HADS scores from baseline to post-treatment time point (approximately 5 weeks interval)
|
|
Psychological Screening Questionnaires (PHQ-9)
Time Frame: changes of PHQ-9 scores from baseline to post-treatment time point (approximately 5 weeks interval)
|
PHQ-9 is used to assess the mental health conditions in the past two weeks.
Total scores of 5, 10, 15, and 20 represent cut points for mild, moderate, moderately severe, and severe depression, respectively.
|
changes of PHQ-9 scores from baseline to post-treatment time point (approximately 5 weeks interval)
|
|
Multidimensional Fatigue Inventory (MFI) Questionnaire
Time Frame: changes of MFI scores from baseline to post-treatment time point (approximately 5 weeks interval)
|
MFI is a 20-item self-report instrument designed to measure fatigue with five dimensions including General Fatigue, Physical Fatigue, Mental Fatigue, Reduced Motivation and Reduced Activity.
Subscale scores (range 4-20) are calculated as the sum of item ratings and a total fatigue score (range 20-100) is calculated as the sum of subscale scores.
Higher scores indicate a higher level of fatigue.
|
changes of MFI scores from baseline to post-treatment time point (approximately 5 weeks interval)
|
|
Pittsburgh Sleep Quality Index (PSQI) Questionnaire
Time Frame: changes of PSQI scores from baseline to post-treatment time point (approximately 5 weeks interval)
|
The PSQI is a 19-item, self-rated questionnaire designed to measure sleep quality and disturbance over the past month in clinical populations.
The sleep component scores are summed to yield a total score ranging from 0 to 21 with the higher total score (referred to as global score) indicating worse sleep quality.
|
changes of PSQI scores from baseline to post-treatment time point (approximately 5 weeks interval)
|
|
Adult Sickle Cell Quality Measure (ASCQ-ME) Questionnaire
Time Frame: changes of pain-related quality of life scores from baseline to post-treatment time point (approximately 5 weeks interval), as well as monthly follow-up visits till the 12th month of last in-person visit.
|
ASCQ-Me contains both questionnaires of pain episodes frequency, severity, and the pain impact that can comprehensively examine the disease severity and impact in pain, stiffness, sleep, social function in patients with SCD.
Scores for ASCQ-Me impact scales range from 0 to 100, with a standardized SCD population mean of 50 (SD, 10), where lower scores connote worse disease impact.
|
changes of pain-related quality of life scores from baseline to post-treatment time point (approximately 5 weeks interval), as well as monthly follow-up visits till the 12th month of last in-person visit.
|
|
Pediatric Quality of Life Inventory (PedsQL, both pediatric and adult versions) Questionnaire
Time Frame: changes of pain-related quality of life scores from baseline to post-treatment time point (approximately 5 weeks interval), as well as monthly follow-up visits till the 12th month of last in-person visit.
|
The PedsQL is a self-report and parent-report measure assessing the quality of life in a variety of domains including physical, emotional, social, and school.
Items are reverse-scored and transformed to a 0-100 scale where higher scores indicate better quality of life.
|
changes of pain-related quality of life scores from baseline to post-treatment time point (approximately 5 weeks interval), as well as monthly follow-up visits till the 12th month of last in-person visit.
|
|
Patient-Reported Outcomes Measurement Information System (PROMIS)-29 Questionnaire
Time Frame: changes of PROMIS-29 scores from baseline to post-treatment time point (approximately 5 weeks interval)
|
The PROMIS-29 has seven health domains (physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, and sleep disturbance) with customized 29-item questions and a single 4-20 numeric rating for each question.
|
changes of PROMIS-29 scores from baseline to post-treatment time point (approximately 5 weeks interval)
|
Other Outcome Measures
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Circulating biomarkers' profile and levels
Time Frame: changes of circulating biomarkers levels from baseline to post-treatment time point (approximately 5 weeks interval)
|
Circulating biomarkers' expression profile and quantitative level of each targeted biomarker in blood samples will be examined using proteomics, multiplex assays, ELISA and etc.
|
changes of circulating biomarkers levels from baseline to post-treatment time point (approximately 5 weeks interval)
|
|
Blood hemoglobin level
Time Frame: changes of blood hemoglobin level from baseline to post-treatment time point (approximately 5 weeks interval)
|
Blood hemoglobin level will be assessed by both regular blood sample analysis and a patented algorithm of spectral super-resolution spectroscopy technique using a software installed smartphone through the participants' inner eyelid.
|
changes of blood hemoglobin level from baseline to post-treatment time point (approximately 5 weeks interval)
|
|
Brain hemodynamic activity
Time Frame: changes of brain hemodynamic activity from baseline to post-treatment time point (approximately 5 weeks interval)
|
Brain hemodynamic activity will be recorded and examined by functional near-infrared spectroscopy.
|
changes of brain hemodynamic activity from baseline to post-treatment time point (approximately 5 weeks interval)
|
|
Brain structural characteristics
Time Frame: changes of brain structural characteristics from baseline to post-treatment time point (approximately 5 weeks interval)
|
Brain structural features will also be examined using MRI.
|
changes of brain structural characteristics from baseline to post-treatment time point (approximately 5 weeks interval)
|
|
brain electrophysiological characteristics: EEG power in alpha band
Time Frame: changes of alpha band from baseline to post-treatment time point (approximately 5 weeks interval)
|
Brain electrophysiological signals will be recorded and examined by EEG.
EEG power in alpha band will be analyzed using Matlab, EEGLab or other computer software designed for EEG data.
|
changes of alpha band from baseline to post-treatment time point (approximately 5 weeks interval)
|
|
brain electrophysiological characteristics: EEG power in theta band
Time Frame: changes of theta band from baseline to post-treatment time point (approximately 5 weeks interval)
|
Brain electrophysiological signals will be recorded and examined by EEG.
EEG power in theta band will be analyzed using Matlab, EEGLab or other computer software designed for EEG data.
|
changes of theta band from baseline to post-treatment time point (approximately 5 weeks interval)
|
|
brain electrophysiological characteristics: EEG power in beta band
Time Frame: changes of beta band from baseline to post-treatment time point (approximately 5 weeks interval)
|
Brain electrophysiological signals will be recorded and examined by EEG.
EEG power in beta band will be analyzed using Matlab, EEGLab or other computer software designed for EEG data.
|
changes of beta band from baseline to post-treatment time point (approximately 5 weeks interval)
|
|
brain electrophysiological characteristics: EEG power in delta band
Time Frame: changes of delta band from baseline to post-treatment time point (approximately 5 weeks interval)
|
Brain electrophysiological signals will be recorded and examined by EEG.
EEG power in delta band will be analyzed using Matlab, EEGLab or other computer software designed for EEG data.
|
changes of delta band from baseline to post-treatment time point (approximately 5 weeks interval)
|
Collaborators and Investigators
Sponsor
Sponsor
Collaborators
Collaborators
Publications and helpful links
General Publications
- Wang Y, Hardy SJ, Ichesco E, Zhang P, Harris RE, Darbari DS. Alteration of grey matter volume is associated with pain and quality of life in children with sickle cell disease. Transl Res. 2022 Feb;240:17-25. doi: 10.1016/j.trsl.2021.08.004. Epub 2021 Aug 19.
- TJ Barrett, A Pucka, B Reyes, SA Jacob, ARW O'Brien, RE Harris, SE Harte, Y Wang*. Acupuncture Alleviates Pain and Improves Quality of Life in Patients with Sickle Cell Disease. Blood. (2022);140 (Supplement 1):5444-5445. (https://doi.org/10.1182/blood-2022-169013)
- JX Yao, ARW O'Brien, YJ Tong*, Y Wang*. A Novel Finding in Cerebral Blood Flow in Patients with Sickle Cell Disease Using Bold Functional MRI. Blood (2022) 140 (Supplement 1): 5433-5434. (https://doi.org/10.1182/blood-2022-167594)
- SM Park, YY Ji, S Kwon, ARW O'Brien, Y Wang*, YL Kim*. Association of Noninvasive Peripheral Blood Hemoglobin Assessments with Venous Blood Draws Among Sickle Cell Patients. Blood (2022) 140 (Supplement 1): 7832-7833. (https://doi.org/10.1182/blood-2022-165132)
- Li W, Pucka AQ, Debats C, Reyes BA, Syed F, O'Brien ARW, Mehta R, Manchanda N, Jacob SA, Hardesty BM, Greist A, Harte SE, Harris RE, Yu Q, Wang Y. Inflammation and autoimmunity are interrelated in patients with sickle cell disease at a steady-state condition: implications for vaso-occlusive crisis, pain, and sensory sensitivity. Front Immunol. 2024 Feb 1;15:1288187. doi: 10.3389/fimmu.2024.1288187. eCollection 2024.
- Joo P, Kim M, Kish B, Nair VV, Tong Y, Liu Z, O'Brien ARW, Harte SE, Harris RE, Lee U, Wang Y. Brain network hypersensitivity underlies pain crises in sickle cell disease. Sci Rep. 2024 Mar 27;14(1):7315. doi: 10.1038/s41598-024-57473-5.
- Zhou X, Ichesco E, Pucka AQ, Liu Z, O'Brien AR, Harte SE, Harris RE, Wang Y. Elevated posterior insula glutamate in patients with sickle cell disease. J Pain. 2025 Feb;27:104743. doi: 10.1016/j.jpain.2024.104743. Epub 2024 Nov 28.
- W Li, AQ Pucka, L Houran, XQ Huang, C Debats, B Reyes, AR O'Brien, QG Yu*, Y Wang* . Soluble immune checkpoint landscape in sickle cell disease links systemic inflammation, autoimmunity, and pain. Frontiers of Hematology (2025). Doi: 10.3389/fihem.2025.1580009.
- Kish B, Yao JF, Frels AJ, Budde J, Vijayakrishnan Nair V, Pucka AQ, Liu Z, O'Brien AR, Tong Y, Wang Y. Novel identifications of cerebral hemodynamics using BOLD fMRI in patients with sickle cell disease. Imaging Neurosci (Camb). 2025 May 16;3:IMAG.a.1. doi: 10.1162/IMAG.a.1. eCollection 2025.
- Wang Y, Wang DD, Pucka AQ, O'Brien ARW, Harte SE, Harris RE. Differential clinical characteristics across traditional Chinese medicine (TCM) Syndromes in patients with sickle cell disease. Front Pain Res (Lausanne). 2024 Jan 5;4:1233293. doi: 10.3389/fpain.2023.1233293. eCollection 2023.
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Study Start
Primary Completion (Actual)
Primary Completion
Study Completion (Estimated)
Study Completion
Study Registration Dates
First Submitted
First Submitted
First Submitted That Met QC Criteria
First Submitted That Met QC Criteria
First Posted (Actual)
First Posted
Study Record Updates
Last Update Posted (Estimated)
Last Update Posted
Last Update Submitted That Met QC Criteria
Last Update Submitted That Met QC Criteria
Last Verified
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neurologic Manifestations
- Genetic Diseases, Inborn
- Hematologic Diseases
- Anemia, Hemolytic, Congenital
- Anemia, Hemolytic
- Anemia
- Hemoglobinopathies
- Congenital, Hereditary, and Neonatal Diseases and Abnormalities
- Pathological Conditions, Signs and Symptoms
- Signs and Symptoms
- Hemic and Lymphatic Diseases
- Pain
- Anemia, Sickle Cell
Other Study ID Numbers
Other Study ID Numbers
- 10056a
- 5R00AT010012 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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