Back Pain, Chronic Pain, Pain
Conditions
Keywords
transcranial magnetic stimulation, resting state MRI
Brief summary
In this study the investigators aim to examine the effects of Transcranial Magnetic Stimulation (TMS) on hippocampal network connectivity and pain levels in individuals with chronic low back pain.
Interventions
DEVICETranscranial Magnetic Stimulation
For the brain stimulation the investigators will use Repetitive Transcranial Magnetic stimulation (rTMS). Different stimulation conditions (hippocampal or sham) will be delivered in each round of stimulation (5 days). Repetitive TMS will be applied at 100% resting motor threshold intensity, 20 Hz pulse trains separated by 28-s inter-train intervals (\ 20 minutes for the entire daily stimulation session). Stimulation parameters will be identical in both groups
DEVICESham rTMS
Sham rTMS
Sponsors
National Institutes of Health (NIH)
National Institute on Drug Abuse (NIDA)
Northwestern University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Intervention model description
All participants will receive the 2 modalities of stimulation (hippocampal and sham-TMS). Each stimulation round is composed by 5 daily sessions of stimulation, participants will not know which round is active and which is sham. The order of the stimulation modalities will be different across subjects. Subjects will be randomly assigned to one of two possible modality order according to the entrance in the study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ≥ 6 months of back pain on a daily basis; * male or female with no racial or ethnic restrictions; * 18 to 75 years old; * average back pain intensity \> 4/10 at study entry; * must be able to read, understand, and sign consent form; * generally healthy.
Exclusion criteria
* back pain with fever, chills, rheumatoid arthritis, ankylosing spondylitis, acute vertebral fractures, * history of tumor in the back; * back surgery within the past 6 months; * Chronic neurologic conditions, e.g., Parkinson's * involvement in litigation regarding back pain; * other severe medical diseases; * pregnancy; * positive urinary screen for any recreational drugs, * opioids use; * use of anticoagulants (low dose ASA allowed); * history of gastric ulcer; renal insufficiency or congestive heart failure, * contraindication to MRI, * contraindication to TMS; including history of seizure/epilepsy\* * Any medical condition that in the investigator's judgment may prevent the individual from completing the study or put the individual at undue risk; * In the judgment of the investigator, unable or unwilling to follow protocol and instructions; * Diagnosis of major depression; * Intra-axial implants (e.g. spinal cord stimulators or pumps)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Pain Scales | Pain is assessed at baseline, end of first intervention and end of the second intervention. | The endpoint will be the severity of pain measured by changes in the Numeric Rating Scale (NRS) scores before and after each stimulation round. The NRS is a pain screening tool that assesses pain severity during assessment using a 0-10 scale, where zero means no pain and ten means the worst pain imaginable. Higher values indicate a worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Hippocampal Connectivity | approximately 6 weeks - Baseline and after the end of hippocampal stimulation | Changes in hippocampal network connectivity will be evaluated by using resting state functional magnetic resonance (fMRI) before and after hippocampal stimulation. Hippocampal connectivity measurements - regions involved in the network and the parietal target - will be compared before stimulation (baseline) to after stimulation (after active hippocampal stimulation). |
Countries
United States
Participant flow
Recruitment details
Participants were screened via a database maintained by one of the co-investigators. The first participant was enrolled on June 25, 2021, and the last participant was enrolled in February 2022.
Pre-assignment details
Of the 44 participants screened, 16 met inclusion criteria and were randomized to treatment.
Participants by arm
| Arm | Count |
|---|---|
| Hippocampus-stimulation First, Then Sham-stimulation Over five consecutive days, we use repetitive transcranial magnetic stimulation (rTMS) at the resting motor threshold intensity to stimulate a region of interest in the parietal cortex, which is determined based on its connectivity with the hippocampus. The rTMS consists of 1,600 pulses delivered in 2-second periods of 20 Hz pulse trains, with 28-second inter-train intervals. Each daily stimulation session lasts about 20 minutes.
After a two-week washout period, we administer sham stimulation with identical parameters except that the coil is flipped over to the sham side, and a stimulating electrode is attached to the skin near the parietal rTMS target location. This electrode delivers a small current to mimic the physical sensation of real stimulation, making it difficult for participants to discriminate between the two types of stimulation. | 5 |
| Sham-stimulation Then Hippocampus Stimulation For five consecutive days, we administer sham stimulation by flipping the coil over to the sham side and attaching a stimulating electrode to the skin near the parietal rTMS target location. The electrode delivers a small current to mimic the physical sensation of real stimulation, making it difficult for participants to distinguish between the two types of stimulation. Each daily stimulation session lasts around 20 minutes.
After a two-week washout period, we use repetitive transcranial magnetic stimulation (rTMS) at the resting motor threshold intensity to stimulate a region of interest in the parietal cortex, which will be determined based on its connectivity with the hippocampus. The rTMS consists of 1,600 pulses delivered in 2-second periods of 20 Hz pulse trains, with 28-second inter-train intervals. | 5 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 3 |
| Overall Study | We dropped the participant due to safety concerns for the staff. | 1 | 0 |
Baseline characteristics
| Characteristic | Hippocampus-stimulation First, Then Sham-stimulation | Sham-stimulation Then Hippocampus Stimulation | Total |
|---|---|---|---|
| Age, Continuous | 58 years STANDARD_DEVIATION 18 | 52 years STANDARD_DEVIATION 15 | 55 years STANDARD_DEVIATION 16 |
| Baseline Pain | 4.6 units on a scale STANDARD_DEVIATION 1.9 | 4.6 units on a scale STANDARD_DEVIATION 1.8 | 4.6 units on a scale STANDARD_DEVIATION 1.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 3 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 3 Participants | 2 Participants | 5 Participants |
| Region of Enrollment United States | 5 participants | 5 participants | 10 participants |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 6 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
Changes in Pain Scales
The endpoint will be the severity of pain measured by changes in the Numeric Rating Scale (NRS) scores before and after each stimulation round. The NRS is a pain screening tool that assesses pain severity during assessment using a 0-10 scale, where zero means no pain and ten means the worst pain imaginable. Higher values indicate a worse outcome.
Time frame: Pain is assessed at baseline, end of first intervention and end of the second intervention.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hippocampus-stimulation | Changes in Pain Scales | Baseline | 4.6 units on a scale | Standard Deviation 1.9 |
| Hippocampus-stimulation | Changes in Pain Scales | After Intervention | 4 units on a scale | Standard Deviation 2.2 |
| Sham-stimulation | Changes in Pain Scales | Baseline | 4.6 units on a scale | Standard Deviation 1.9 |
| Sham-stimulation | Changes in Pain Scales | After Intervention | 4.4 units on a scale | Standard Deviation 1.8 |
Secondary
Changes in Hippocampal Connectivity
Changes in hippocampal network connectivity will be evaluated by using resting state functional magnetic resonance (fMRI) before and after hippocampal stimulation. Hippocampal connectivity measurements - regions involved in the network and the parietal target - will be compared before stimulation (baseline) to after stimulation (after active hippocampal stimulation).
Time frame: approximately 6 weeks - Baseline and after the end of hippocampal stimulation
Population: The data was not collected due to the COVID-19 pandemic.