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Enhancing Acupuncture Treatment Effect Through Non-invasive Neuromodulation

Enhancing Acupuncture Treatment Effect Through Non-invasive Neuromodulation

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03716830
Enrollment
116
Registered
2018-10-23
Start date
2020-11-07
Completion date
2025-03-31
Last updated
2025-11-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Pain

Brief summary

In this study, investigators will examine the brain mechanism behind the synergistic effects of combining acupuncture and transcranial direct current stimulation (tDCS) treatments. Specifically, chronic low back pain (cLBP) patients will be recruited and randomized to one of four groups (30 per group, one month of treatment): 1) verum acupuncture + real tDCS, 2) sham acupuncture + real tDCS, 3) verum acupuncture + sham tDCS, and 4) sham acupuncture + sham tDCS. Investigators will study 1) the longitudinal (one-month) effects of different treatments as indicated by changes in resting state functional connectivity (rsFC), cerebral blood flow (CBF), clinical outcomes of low back pain, and quantitative sensory test (QST) and 2) the association between these changes.

Interventions

Participants will receive real acupuncture treatment.

DEVICEsham acupuncture

Participants will receive sham acupuncture treatment.

DEVICEreal tDCS

Participants will receive real transcranial direct current stimulation.

DEVICEsham tDCS

Participants will receive sham transcranial direct current stimulation.

Sponsors

Massachusetts General Hospital
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)

Masking description

Both participants and study staff will be blinded to the treatment group of participants. Only the licensed acupuncturist will be aware of the type of acupuncture the participant will be receiving.

Intervention model description

Participants will be randomized to one of four groups: 1) verum acupuncture + real tDCS, 2) sham acupuncture + real tDCS, 3) verum acupuncture + sham tDCS, and 4) sham acupuncture + sham tDCS.

Eligibility

Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No

Inclusion criteria

* volunteers 18-60 years of age * meet the classification criteria of chronic low back pain (having low back pain for more than 6 months), as determined by the referring physician * at least 4/10 clinical pain on the 11-point Low Back Pain Numeric Rating Scale (LBP NRS) * at least a 10th grade English-reading level; English can be a second language provided that the patients understand all questions used in the assessment measures

Exclusion criteria

* history of epilepsy or loss consciousness (LOC) * specific causes of back pain (e.g. cancer, fractures, spinal stenosis, infections) * complicated back problems (e.g. prior back surgery, medicolegal issues) * the intent to undergo surgery during the time of involvement in the study * history of cardiac, respiratory, or nervous system disease that, in the investigator's judgment, precludes participation in the study because of a heightened potential for adverse outcomes. For example: asthma or claustrophobia * presence of any contraindications to magnetic resonance imaging (MRI) scanning. For example: cardiac pacemaker, metal implants, claustrophobia, pregnancy, inability to remain still in MRI scanner * history of medical or psychiatric illness as determined by the investigator * history of substance abuse or dependence

Design outcomes

Primary

MeasureTime frameDescription
Periaqueductal Gray (PAG) Resting State Functional Connectivity (rsFC) Changesdifference between Day 1 (pre-intervention); post-intervention at Week 4 (pre-intervention - Post-intervention)We investigated whether tDCS and acupuncture treatments modulate resting-state functional connectivity (rsFC) of the periaqueductal gray (PAG). This was evaluated by comparing pre- and post-treatment MRI scans. In this report, we focused on the rsFC between the PAG and the rostral anterior cingulate cortex (rACC, peak MNI coordinate (2, 38, 12) with a 2-mm radius sphere). Functional connectivity values were computed as Pearson's correlation coefficients between the mean time series of predefined regions of interest (ROIs). To improve normality and enable parametric statistical analysis, these correlation coefficients (r) were converted to Fisher z values using the transformation z = 0.5 × ln\[(1 + r) / (1 - r)\]. Higher Fisher z values indicate stronger positive connectivity, whereas lower values indicate weaker or negative connectivity. Changes in Fisher z values from baseline to post-intervention reflect the degree and direction of connectivity modulation.

Secondary

MeasureTime frameDescription
Clinical Outcomes as Measured by LBP Intensity ScoresDifference between the Day 1 (pre-intervention) and post-intervention at Week 4 (post-intervention - pre-intervention)The Low Back Pain Numeric Rating Scale (LBP NRS) is a standardized adaptation of the Pain Numeric Rating Scale for assessing pain intensity specifically related to the lower back. It uses an 11-point scale from 0 (no low back pain) to 10 (worst low back pain imaginable), allowing patients to rate their pain over the past week.
Cerebral Blood Flow (CBF) Differences Before and After TreatmentsDay 1 (pre-intervention); post-intervention at Week 4Investigators will examine Cerebral blood flow (CBF) changes before and after treatment in several pain-related brain areas. Cerebral blood flow represents the volume of blood delivered to brain tissue per unit time, CBF data will be collected during arterial spin labeling (ASL) scans that will take place before the first treatment and after the last treatment. Images from these scans will be aggregated to an average CBF-weighted image to be used for analysis. In this report, we focused on bilateral postcentral Gyrus (MNI coordinate: +/-18, -34, 56, 2 mm sphere)
Quantitative Sensory Testing (QST) DifferencesDay 1 (pre-intervention); post-intervention at Week 4 (pre-intervention - post-intervention)Participants' quantitative sensory testing (QST) ratings were analyzed before and after all treatments. Here, we report the heat pain threshold measured around the affected lower back area.
Primary Motor Cortex (M1) rsFC Changes Before and After 4-week TreatmentsDay 1 (pre-intervention); post-intervention at Week 4 (pre-intervention - post-intervention)We investigated whether tDCS and acupuncture treatments modulate resting-state functional connectivity (rsFC) of the M1. This was evaluated by comparing pre- and post-treatment MRI scans. In this report, we focused on the rsFC between the PAG and the rostral anterior cingulate cortex (rACC), using a seed defined by the rACC peak MNI coordinate (0, 34, 20) with a 2-mm radius sphere. Functional connectivity values were computed as Pearson's correlation coefficients between the mean time series of predefined regions of interest (ROIs). To improve normality and enable parametric statistical analysis, these correlation coefficients (r) were converted to Fisher z values using the transformation z = 0.5 × ln\[(1 + r) / (1 - r)\]. Higher Fisher z values indicate stronger positive connectivity, whereas lower values indicate weaker or negative connectivity. Changes in Fisher z values from baseline to post-intervention

Countries

United States

Participant flow

Recruitment details

The recruitment started on Nov, 07, 2020. The study was conducted at Massachusetts General Hospital.

Participants by arm

ArmCount
Verum Acupuncture + Real tDCS
verum acupuncture: Participants will receive real acupuncture treatment. real tDCS: Participants will receive real transcranial direct current stimulation.
27
Sham Acupuncture + Real tDCS
sham acupuncture: Participants will receive sham acupuncture treatment. real tDCS: Participants will receive real transcranial direct current stimulation.
25
Verum Acupuncture + Sham tDCS
verum acupuncture: Participants will receive real acupuncture treatment. sham tDCS: Participants will receive sham transcranial direct current stimulation.
20
Sham Acupuncture + Sham tDCS
sham acupuncture: Participants will receive sham acupuncture treatment. sham tDCS: Participants will receive sham transcranial direct current stimulation.
23
Total95

Withdrawals & dropouts

PeriodReasonFG000FG001FG002FG003
Overall StudyAdverse Event1201
Overall StudyLost to Follow-up1100
Overall StudyWithdrawal by Subject2265

Baseline characteristics

CharacteristicSham Acupuncture + Real tDCSVerum Acupuncture + Sham tDCSSham Acupuncture + Sham tDCSTotalVerum Acupuncture + Real tDCS
Age, Continuous38 years
STANDARD_DEVIATION 13
41 years
STANDARD_DEVIATION 13
42 years
STANDARD_DEVIATION 12
41 years
STANDARD_DEVIATION 13
43 years
STANDARD_DEVIATION 13
Race/Ethnicity, Customized
Asian
5 Participants2 Participants2 Participants11 Participants2 Participants
Race/Ethnicity, Customized
Black or African
2 Participants4 Participants2 Participants12 Participants4 Participants
Race/Ethnicity, Customized
Other
0 Participants2 Participants1 Participants4 Participants1 Participants
Race/Ethnicity, Customized
Unknown/not-reported
0 Participants1 Participants3 Participants5 Participants1 Participants
Race/Ethnicity, Customized
White
18 Participants11 Participants15 Participants63 Participants19 Participants
Region of Enrollment
United States
25 participants20 participants23 participants95 participants27 participants
Sex: Female, Male
Female
14 Participants10 Participants11 Participants48 Participants13 Participants
Sex: Female, Male
Male
11 Participants10 Participants12 Participants47 Participants14 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
deaths
Total, all-cause mortality
0 / 270 / 250 / 200 / 23
other
Total, other adverse events
0 / 271 / 250 / 203 / 23
serious
Total, serious adverse events
0 / 270 / 250 / 200 / 23

Outcome results

Primary

Periaqueductal Gray (PAG) Resting State Functional Connectivity (rsFC) Changes

We investigated whether tDCS and acupuncture treatments modulate resting-state functional connectivity (rsFC) of the periaqueductal gray (PAG). This was evaluated by comparing pre- and post-treatment MRI scans. In this report, we focused on the rsFC between the PAG and the rostral anterior cingulate cortex (rACC, peak MNI coordinate (2, 38, 12) with a 2-mm radius sphere). Functional connectivity values were computed as Pearson's correlation coefficients between the mean time series of predefined regions of interest (ROIs). To improve normality and enable parametric statistical analysis, these correlation coefficients (r) were converted to Fisher z values using the transformation z = 0.5 × ln\[(1 + r) / (1 - r)\]. Higher Fisher z values indicate stronger positive connectivity, whereas lower values indicate weaker or negative connectivity. Changes in Fisher z values from baseline to post-intervention reflect the degree and direction of connectivity modulation.

Time frame: difference between Day 1 (pre-intervention); post-intervention at Week 4 (pre-intervention - Post-intervention)

Population: Individuals with chronic low back pain

ArmMeasureValue (MEAN)Dispersion
Verum Acupuncture + Real tDCSPeriaqueductal Gray (PAG) Resting State Functional Connectivity (rsFC) Changes-0.03 Fisher z-transformed correlation coefficStandard Deviation 0.16
Sham Acupuncture + Real tDCSPeriaqueductal Gray (PAG) Resting State Functional Connectivity (rsFC) Changes0.02 Fisher z-transformed correlation coefficStandard Deviation 0.17
Verum Acupuncture + Sham tDCSPeriaqueductal Gray (PAG) Resting State Functional Connectivity (rsFC) Changes0.11 Fisher z-transformed correlation coefficStandard Deviation 0.1
Sham Acupuncture + Sham tDCSPeriaqueductal Gray (PAG) Resting State Functional Connectivity (rsFC) Changes-0.03 Fisher z-transformed correlation coefficStandard Deviation 0.11
Secondary

Cerebral Blood Flow (CBF) Differences Before and After Treatments

Investigators will examine Cerebral blood flow (CBF) changes before and after treatment in several pain-related brain areas. Cerebral blood flow represents the volume of blood delivered to brain tissue per unit time, CBF data will be collected during arterial spin labeling (ASL) scans that will take place before the first treatment and after the last treatment. Images from these scans will be aggregated to an average CBF-weighted image to be used for analysis. In this report, we focused on bilateral postcentral Gyrus (MNI coordinate: +/-18, -34, 56, 2 mm sphere)

Time frame: Day 1 (pre-intervention); post-intervention at Week 4

Population: chronic low back pain patients

ArmMeasureValue (MEAN)Dispersion
Verum Acupuncture + Real tDCSCerebral Blood Flow (CBF) Differences Before and After Treatments3.3 mL/sStandard Deviation 9.7
Sham Acupuncture + Real tDCSCerebral Blood Flow (CBF) Differences Before and After Treatments-2.8 mL/sStandard Deviation 9.6
Verum Acupuncture + Sham tDCSCerebral Blood Flow (CBF) Differences Before and After Treatments2.7 mL/sStandard Deviation 4.7
Sham Acupuncture + Sham tDCSCerebral Blood Flow (CBF) Differences Before and After Treatments3.9 mL/sStandard Deviation 17.9
Secondary

Clinical Outcomes as Measured by LBP Intensity Scores

The Low Back Pain Numeric Rating Scale (LBP NRS) is a standardized adaptation of the Pain Numeric Rating Scale for assessing pain intensity specifically related to the lower back. It uses an 11-point scale from 0 (no low back pain) to 10 (worst low back pain imaginable), allowing patients to rate their pain over the past week.

Time frame: Difference between the Day 1 (pre-intervention) and post-intervention at Week 4 (post-intervention - pre-intervention)

Population: individuals with chronic low back pain

ArmMeasureValue (MEAN)
Verum Acupuncture + Real tDCSClinical Outcomes as Measured by LBP Intensity Scores-1.39 score on a scale
Sham Acupuncture + Real tDCSClinical Outcomes as Measured by LBP Intensity Scores-1.08 score on a scale
Verum Acupuncture + Sham tDCSClinical Outcomes as Measured by LBP Intensity Scores-1.45 score on a scale
Sham Acupuncture + Sham tDCSClinical Outcomes as Measured by LBP Intensity Scores-1.59 score on a scale
Secondary

Primary Motor Cortex (M1) rsFC Changes Before and After 4-week Treatments

We investigated whether tDCS and acupuncture treatments modulate resting-state functional connectivity (rsFC) of the M1. This was evaluated by comparing pre- and post-treatment MRI scans. In this report, we focused on the rsFC between the PAG and the rostral anterior cingulate cortex (rACC), using a seed defined by the rACC peak MNI coordinate (0, 34, 20) with a 2-mm radius sphere. Functional connectivity values were computed as Pearson's correlation coefficients between the mean time series of predefined regions of interest (ROIs). To improve normality and enable parametric statistical analysis, these correlation coefficients (r) were converted to Fisher z values using the transformation z = 0.5 × ln\[(1 + r) / (1 - r)\]. Higher Fisher z values indicate stronger positive connectivity, whereas lower values indicate weaker or negative connectivity. Changes in Fisher z values from baseline to post-intervention

Time frame: Day 1 (pre-intervention); post-intervention at Week 4 (pre-intervention - post-intervention)

Population: low back pain patients

ArmMeasureValue (MEAN)Dispersion
Verum Acupuncture + Real tDCSPrimary Motor Cortex (M1) rsFC Changes Before and After 4-week Treatments0.14 Fisher z-transformed correlation coefficStandard Deviation 0.14
Sham Acupuncture + Real tDCSPrimary Motor Cortex (M1) rsFC Changes Before and After 4-week Treatments-0.01 Fisher z-transformed correlation coefficStandard Deviation 0.18
Verum Acupuncture + Sham tDCSPrimary Motor Cortex (M1) rsFC Changes Before and After 4-week Treatments-0.03 Fisher z-transformed correlation coefficStandard Deviation 0.16
Sham Acupuncture + Sham tDCSPrimary Motor Cortex (M1) rsFC Changes Before and After 4-week Treatments0 Fisher z-transformed correlation coefficStandard Deviation 0.13
Secondary

Quantitative Sensory Testing (QST) Differences

Participants' quantitative sensory testing (QST) ratings were analyzed before and after all treatments. Here, we report the heat pain threshold measured around the affected lower back area.

Time frame: Day 1 (pre-intervention); post-intervention at Week 4 (pre-intervention - post-intervention)

Population: patients with chronic low back pain

ArmMeasureValue (MEAN)Dispersion
Verum Acupuncture + Real tDCSQuantitative Sensory Testing (QST) Differences-0.2 degrees CelsiusStandard Deviation 2.2
Sham Acupuncture + Real tDCSQuantitative Sensory Testing (QST) Differences1.0 degrees CelsiusStandard Deviation 2
Verum Acupuncture + Sham tDCSQuantitative Sensory Testing (QST) Differences-1 degrees CelsiusStandard Deviation 1.7
Sham Acupuncture + Sham tDCSQuantitative Sensory Testing (QST) Differences-0.6 degrees CelsiusStandard Deviation 2

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026