Trial Outcomes & Findings for Enhancing Acupuncture Treatment Effect Through Non-invasive Neuromodulation (NCT NCT03716830)
NCT ID: NCT03716830
Last Updated: 2025-11-05
Results Overview
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.
COMPLETED
NA
116 participants
difference between Day 1 (pre-intervention); post-intervention at Week 4 (pre-intervention - Post-intervention)
2025-11-05
Participant Flow
The recruitment started on Nov, 07, 2020. The study was conducted at Massachusetts General Hospital.
Participant milestones
| Measure |
Verum Acupuncture + Real tDCS
verum acupuncture: Participants will receive real acupuncture treatment.
real tDCS: Participants will receive real transcranial direct current stimulation.
|
Sham Acupuncture + Real tDCS
sham acupuncture: Participants will receive sham acupuncture treatment.
real tDCS: Participants will receive real transcranial direct current stimulation.
|
Verum Acupuncture + Sham tDCS
verum acupuncture: Participants will receive real acupuncture treatment.
sham tDCS: Participants will receive sham transcranial direct current stimulation.
|
Sham Acupuncture + Sham tDCS
sham acupuncture: Participants will receive sham acupuncture treatment.
sham tDCS: Participants will receive sham transcranial direct current stimulation.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
31
|
30
|
26
|
29
|
|
Overall Study
COMPLETED
|
27
|
25
|
20
|
23
|
|
Overall Study
NOT COMPLETED
|
4
|
5
|
6
|
6
|
Reasons for withdrawal
| Measure |
Verum Acupuncture + Real tDCS
verum acupuncture: Participants will receive real acupuncture treatment.
real tDCS: Participants will receive real transcranial direct current stimulation.
|
Sham Acupuncture + Real tDCS
sham acupuncture: Participants will receive sham acupuncture treatment.
real tDCS: Participants will receive real transcranial direct current stimulation.
|
Verum Acupuncture + Sham tDCS
verum acupuncture: Participants will receive real acupuncture treatment.
sham tDCS: Participants will receive sham transcranial direct current stimulation.
|
Sham Acupuncture + Sham tDCS
sham acupuncture: Participants will receive sham acupuncture treatment.
sham tDCS: Participants will receive sham transcranial direct current stimulation.
|
|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
2
|
2
|
6
|
5
|
|
Overall Study
Adverse Event
|
1
|
2
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
1
|
0
|
0
|
Baseline Characteristics
Enhancing Acupuncture Treatment Effect Through Non-invasive Neuromodulation
Baseline characteristics by cohort
| Measure |
Verum Acupuncture + Real tDCS
n=27 Participants
verum acupuncture: Participants will receive real acupuncture treatment.
real tDCS: Participants will receive real transcranial direct current stimulation.
|
Sham Acupuncture + Real tDCS
n=25 Participants
sham acupuncture: Participants will receive sham acupuncture treatment.
real tDCS: Participants will receive real transcranial direct current stimulation.
|
Verum Acupuncture + Sham tDCS
n=20 Participants
verum acupuncture: Participants will receive real acupuncture treatment.
sham tDCS: Participants will receive sham transcranial direct current stimulation.
|
Sham Acupuncture + Sham tDCS
n=23 Participants
sham acupuncture: Participants will receive sham acupuncture treatment.
sham tDCS: Participants will receive sham transcranial direct current stimulation.
|
Total
n=95 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
43 years
STANDARD_DEVIATION 13 • n=15 Participants
|
38 years
STANDARD_DEVIATION 13 • n=161 Participants
|
41 years
STANDARD_DEVIATION 13 • n=100 Participants
|
42 years
STANDARD_DEVIATION 12 • n=3 Participants
|
41 years
STANDARD_DEVIATION 13 • n=8 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=15 Participants
|
14 Participants
n=161 Participants
|
10 Participants
n=100 Participants
|
11 Participants
n=3 Participants
|
48 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=15 Participants
|
11 Participants
n=161 Participants
|
10 Participants
n=100 Participants
|
12 Participants
n=3 Participants
|
47 Participants
n=8 Participants
|
|
Race/Ethnicity, Customized
White
|
19 Participants
n=15 Participants
|
18 Participants
n=161 Participants
|
11 Participants
n=100 Participants
|
15 Participants
n=3 Participants
|
63 Participants
n=8 Participants
|
|
Race/Ethnicity, Customized
Black or African
|
4 Participants
n=15 Participants
|
2 Participants
n=161 Participants
|
4 Participants
n=100 Participants
|
2 Participants
n=3 Participants
|
12 Participants
n=8 Participants
|
|
Race/Ethnicity, Customized
Asian
|
2 Participants
n=15 Participants
|
5 Participants
n=161 Participants
|
2 Participants
n=100 Participants
|
2 Participants
n=3 Participants
|
11 Participants
n=8 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=15 Participants
|
0 Participants
n=161 Participants
|
2 Participants
n=100 Participants
|
1 Participants
n=3 Participants
|
4 Participants
n=8 Participants
|
|
Race/Ethnicity, Customized
Unknown/not-reported
|
1 Participants
n=15 Participants
|
0 Participants
n=161 Participants
|
1 Participants
n=100 Participants
|
3 Participants
n=3 Participants
|
5 Participants
n=8 Participants
|
|
Region of Enrollment
United States
|
27 participants
n=15 Participants
|
25 participants
n=161 Participants
|
20 participants
n=100 Participants
|
23 participants
n=3 Participants
|
95 participants
n=8 Participants
|
PRIMARY outcome
Timeframe: difference between Day 1 (pre-intervention); post-intervention at Week 4 (pre-intervention - Post-intervention)Population: Individuals with chronic low back pain
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.
Outcome measures
| Measure |
Sham Acupuncture + Real tDCS
n=23 Participants
sham acupuncture: Participants will receive sham acupuncture treatment.
real tDCS: Participants will receive real transcranial direct current stimulation.
|
Verum Acupuncture + Sham tDCS
n=19 Participants
verum acupuncture: Participants will receive real acupuncture treatment.
sham tDCS: Participants will receive sham transcranial direct current stimulation.
|
Sham Acupuncture + Sham tDCS
n=21 Participants
sham acupuncture: Participants will receive sham acupuncture treatment.
sham tDCS: Participants will receive sham transcranial direct current stimulation.
|
Verum Acupuncture + Real tDCS
n=24 Participants
verum acupuncture: Participants will receive real acupuncture treatment.
real tDCS: Participants will receive real transcranial direct current stimulation.
|
|---|---|---|---|---|
|
Periaqueductal Gray (PAG) Resting State Functional Connectivity (rsFC) Changes
|
0.02 Fisher z-transformed correlation coeffic
Standard Deviation 0.17
|
0.11 Fisher z-transformed correlation coeffic
Standard Deviation 0.1
|
-0.03 Fisher z-transformed correlation coeffic
Standard Deviation 0.11
|
-0.03 Fisher z-transformed correlation coeffic
Standard Deviation 0.16
|
SECONDARY outcome
Timeframe: Difference between the Day 1 (pre-intervention) and post-intervention at Week 4 (post-intervention - pre-intervention)Population: individuals with chronic low back pain
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.
Outcome measures
| Measure |
Sham Acupuncture + Real tDCS
n=25 Participants
sham acupuncture: Participants will receive sham acupuncture treatment.
real tDCS: Participants will receive real transcranial direct current stimulation.
|
Verum Acupuncture + Sham tDCS
n=20 Participants
verum acupuncture: Participants will receive real acupuncture treatment.
sham tDCS: Participants will receive sham transcranial direct current stimulation.
|
Sham Acupuncture + Sham tDCS
n=22 Participants
sham acupuncture: Participants will receive sham acupuncture treatment.
sham tDCS: Participants will receive sham transcranial direct current stimulation.
|
Verum Acupuncture + Real tDCS
n=26 Participants
verum acupuncture: Participants will receive real acupuncture treatment.
real tDCS: Participants will receive real transcranial direct current stimulation.
|
|---|---|---|---|---|
|
Clinical Outcomes as Measured by LBP Intensity Scores
|
-1.08 score on a scale
Interval -1.78 to -0.38
|
-1.45 score on a scale
Interval -2.24 to -0.06
|
-1.59 score on a scale
Interval -2.34 to -0.84
|
-1.39 score on a scale
Interval -2.07 to -0.7
|
SECONDARY outcome
Timeframe: Day 1 (pre-intervention); post-intervention at Week 4Population: chronic low back pain patients
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)
Outcome measures
| Measure |
Sham Acupuncture + Real tDCS
n=19 Participants
sham acupuncture: Participants will receive sham acupuncture treatment.
real tDCS: Participants will receive real transcranial direct current stimulation.
|
Verum Acupuncture + Sham tDCS
n=18 Participants
verum acupuncture: Participants will receive real acupuncture treatment.
sham tDCS: Participants will receive sham transcranial direct current stimulation.
|
Sham Acupuncture + Sham tDCS
n=17 Participants
sham acupuncture: Participants will receive sham acupuncture treatment.
sham tDCS: Participants will receive sham transcranial direct current stimulation.
|
Verum Acupuncture + Real tDCS
n=20 Participants
verum acupuncture: Participants will receive real acupuncture treatment.
real tDCS: Participants will receive real transcranial direct current stimulation.
|
|---|---|---|---|---|
|
Cerebral Blood Flow (CBF) Differences Before and After Treatments
|
-2.8 mL/s
Standard Deviation 9.6
|
2.7 mL/s
Standard Deviation 4.7
|
3.9 mL/s
Standard Deviation 17.9
|
3.3 mL/s
Standard Deviation 9.7
|
SECONDARY outcome
Timeframe: Day 1 (pre-intervention); post-intervention at Week 4 (pre-intervention - post-intervention)Population: patients with chronic low back pain
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.
Outcome measures
| Measure |
Sham Acupuncture + Real tDCS
n=22 Participants
sham acupuncture: Participants will receive sham acupuncture treatment.
real tDCS: Participants will receive real transcranial direct current stimulation.
|
Verum Acupuncture + Sham tDCS
n=19 Participants
verum acupuncture: Participants will receive real acupuncture treatment.
sham tDCS: Participants will receive sham transcranial direct current stimulation.
|
Sham Acupuncture + Sham tDCS
n=20 Participants
sham acupuncture: Participants will receive sham acupuncture treatment.
sham tDCS: Participants will receive sham transcranial direct current stimulation.
|
Verum Acupuncture + Real tDCS
n=25 Participants
verum acupuncture: Participants will receive real acupuncture treatment.
real tDCS: Participants will receive real transcranial direct current stimulation.
|
|---|---|---|---|---|
|
Quantitative Sensory Testing (QST) Differences
|
1.0 degrees Celsius
Standard Deviation 2.0
|
-1 degrees Celsius
Standard Deviation 1.7
|
-0.6 degrees Celsius
Standard Deviation 2
|
-0.2 degrees Celsius
Standard Deviation 2.2
|
SECONDARY outcome
Timeframe: Day 1 (pre-intervention); post-intervention at Week 4 (pre-intervention - post-intervention)Population: low back pain patients
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
Outcome measures
| Measure |
Sham Acupuncture + Real tDCS
n=23 Participants
sham acupuncture: Participants will receive sham acupuncture treatment.
real tDCS: Participants will receive real transcranial direct current stimulation.
|
Verum Acupuncture + Sham tDCS
n=19 Participants
verum acupuncture: Participants will receive real acupuncture treatment.
sham tDCS: Participants will receive sham transcranial direct current stimulation.
|
Sham Acupuncture + Sham tDCS
n=21 Participants
sham acupuncture: Participants will receive sham acupuncture treatment.
sham tDCS: Participants will receive sham transcranial direct current stimulation.
|
Verum Acupuncture + Real tDCS
n=24 Participants
verum acupuncture: Participants will receive real acupuncture treatment.
real tDCS: Participants will receive real transcranial direct current stimulation.
|
|---|---|---|---|---|
|
Primary Motor Cortex (M1) rsFC Changes Before and After 4-week Treatments
|
-0.01 Fisher z-transformed correlation coeffic
Standard Deviation 0.18
|
-0.03 Fisher z-transformed correlation coeffic
Standard Deviation 0.16
|
0 Fisher z-transformed correlation coeffic
Standard Deviation 0.13
|
0.14 Fisher z-transformed correlation coeffic
Standard Deviation 0.14
|
Adverse Events
Verum Acupuncture + Real tDCS
Sham Acupuncture + Real tDCS
Verum Acupuncture + Sham tDCS
Sham Acupuncture + Sham tDCS
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Verum Acupuncture + Real tDCS
n=27 participants at risk
verum acupuncture: Participants will receive real acupuncture treatment.
real tDCS: Participants will receive real transcranial direct current stimulation.
|
Sham Acupuncture + Real tDCS
n=25 participants at risk
sham acupuncture: Participants will receive sham acupuncture treatment.
real tDCS: Participants will receive real transcranial direct current stimulation.
|
Verum Acupuncture + Sham tDCS
n=20 participants at risk
verum acupuncture: Participants will receive real acupuncture treatment.
sham tDCS: Participants will receive sham transcranial direct current stimulation.
|
Sham Acupuncture + Sham tDCS
n=23 participants at risk
sham acupuncture: Participants will receive sham acupuncture treatment.
sham tDCS: Participants will receive sham transcranial direct current stimulation.
|
|---|---|---|---|---|
|
Nervous system disorders
Headache
|
0.00%
0/27 • from baseline to post-intervention assessments, up to 6 weeks
Same as clinicaltrials.gov definition
|
0.00%
0/25 • from baseline to post-intervention assessments, up to 6 weeks
Same as clinicaltrials.gov definition
|
0.00%
0/20 • from baseline to post-intervention assessments, up to 6 weeks
Same as clinicaltrials.gov definition
|
8.7%
2/23 • Number of events 2 • from baseline to post-intervention assessments, up to 6 weeks
Same as clinicaltrials.gov definition
|
|
General disorders
Needle pain discomfort
|
0.00%
0/27 • from baseline to post-intervention assessments, up to 6 weeks
Same as clinicaltrials.gov definition
|
4.0%
1/25 • Number of events 2 • from baseline to post-intervention assessments, up to 6 weeks
Same as clinicaltrials.gov definition
|
0.00%
0/20 • from baseline to post-intervention assessments, up to 6 weeks
Same as clinicaltrials.gov definition
|
0.00%
0/23 • from baseline to post-intervention assessments, up to 6 weeks
Same as clinicaltrials.gov definition
|
|
General disorders
Neck pain
|
0.00%
0/27 • from baseline to post-intervention assessments, up to 6 weeks
Same as clinicaltrials.gov definition
|
0.00%
0/25 • from baseline to post-intervention assessments, up to 6 weeks
Same as clinicaltrials.gov definition
|
0.00%
0/20 • from baseline to post-intervention assessments, up to 6 weeks
Same as clinicaltrials.gov definition
|
4.3%
1/23 • Number of events 1 • from baseline to post-intervention assessments, up to 6 weeks
Same as clinicaltrials.gov definition
|
Additional Information
Jian Kong, PI of the clinical trial
Massachusetts General Hospital
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place