Back Ache, Back Pain Lower Back Chronic, Back Pain Without Radiation, Back Pain With Radiation, Low Back Pain, Pain, Chronic
Conditions
Keywords
Microglia, Minocycline, Magnetic Resonance Imaging, Positron Emission Tomography, Pain, Astrocytes, Glia, Human, Back Pain
Brief summary
In this research, the study team will use brain imaging to evaluate the presence of neuroinflammation in the brains and spinal cords of patients with low back pain. The efficacy of minocycline use for low back pain treatment will also be evaluated by observing whether short-term minocycline administration will reduce neuroinflammation and low back pain symptoms.
Detailed description
The goal of this research study is to evaluate whether the central nervous systems of those with low back pain are different from those of healthy, pain-free individuals. Specifically, the researchers will test whether "glial cells" (the immune cells of the brain and spinal cord) are more active in patients with low back pain than in healthy volunteers. The investigators' previous study showed that patients with chronic low back pain demonstrated elevations in brain levels of the 18kDa translocator protein (TSPO), a marker of glial activation. To test this hypothesis, the study team will image the brains and spinal cords of patients suffering from low back pain using integrated magnetic resonance- positron emission tomography (MR-PET), and a radiotracer called \[11C\]PBR28, which tracks levels of glial activation. The efficacy of minocycline as a treatment for chronic low back pain will also be evaluated. A recent study demonstrated a statistically significant reduction in pain in those with lumbar radiculopathy after treatment with minocycline, leading the investigators of this study to believe that minocycline may have potential efficacy in treating other back pain populations. The study team will observe whether a short course of minocycline hydrochloride may reduce glial activation along with self-reported low back pain symptoms. To this end, patients will be evaluated clinically and/or re-scanned after completing a 2-week trial of minocycline or placebo (a sugar pill). This study will be enrolling individuals who have been suffering from sub-acute (short-term) and chronic low back pain.
Interventions
DRUGMinocycline Hydrochloride 100mg Capsule
Minocycline 100mg will be administered by mouth daily for 2 weeks
DIAGNOSTIC_TESTMagnetic Resonance-Positron Emission Tomography Imaging
Up to 15 millicuries of \[11C\]PBR28 will be administered to each subject at each imaging visit, for a maximum of 2 imaging visits.
OTHERPlacebo Capsule
1 Placebo Capsule (compounded with lactose powder) will be administered by mouth daily for 2 weeks
Sponsors
Marco Loggia
National Institute of Neurological Disorders and Stroke (NINDS)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* the ability to give written informed consent * fluency in English * on a stable pain treatment * Chronic or sub-acute low back pain
Exclusion criteria
* no interventional pain procedures during drug trial * contraindications to MRI and PET scanning (including presence of a cardiac pacemaker or pacemaker wires, metallic particles in the body, vascular clips in the head or previous neurosurgery, prosthetic heart valves, claustrophobia) * pregnancy or breast feeding * any use of recreational drugs in the past 6 months * allergy to minocycline or other tetracyclines, or taking medications known to interact with minocycline * any other contraindications to minocycline administration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Thalamic Standardized Uptake Value Ratio (SUVR) | The outcome measure was assessed in two time points, before and after a two-week treatment period. | The ratio of the standardized uptake value (SUV; mean radioactivity divided by the injected dose by weight) of the whole thalamus divided by the SUV of the whole brain (i.e., standardized uptake value ratio or SUVR) derived from the translocator protein positron emission tomography (TSPO-PET) signal. Higher SUVR might be indicative of higher neuroinflammation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Spinal PET Signal | 2 weeks | The standardized uptake value (SUV; mean radioactivity divided by the injected dose by weight) of the spine derived from the translocator protein positron emission tomography (TSPO-PET) signal. A higher SUV might be indicative of greater neuroinflammation. |
| Rate of Change in Daily Modified Brief Pain Inventory (BPI) Severity Subscale | 2 weeks | Estimated Mean Rate of Change of BPI per Day, separately by Treatment Group (Minocycline vs. Placebo), measured as Slope of Change over Time |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMarco L Loggia, PhD
Massachusetts General Hospital
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Minocycline Arm Evaluation with Magnetic Resonance-Positron Emission Tomography Imaging and/or behavioral pain assessment before and after a 2-week trial of Minocycline Hydrochloride, 100mg capsule.
Minocycline Hydrochloride 100mg Capsule: Minocycline administered by mouth daily for 2 weeks
Magnetic Resonance-Positron Emission Tomography Imaging: Up to 15 millicuries of \[11C\]PBR28 administered to each subject at each imaging visit, for a maximum of 2 imaging visits. | 25 |
| Placebo Arm Evaluation with Magnetic Resonance-Positron Emission Tomography Imaging and/or behavioral pain assessment before and after 2 weeks of treatment with a placebo capsule.
Placebo Capsule: Placebo (lactose powder) administered by mouth daily for 2 weeks.
Magnetic Resonance-Positron Emission Tomography Imaging: Up to 15 millicuries of \[11C\]PBR28 administered to each subject at each imaging visit, for a maximum of 2 imaging visits. | 23 |
| Total | 48 |
Baseline characteristics
| Characteristic | Minocycline Arm | Placebo Arm | Total |
|---|---|---|---|
| Age, Continuous | 44.6 Years STANDARD_DEVIATION 16.9 | 49 Years STANDARD_DEVIATION 17.1 | 45.9 Years STANDARD_DEVIATION 16.1 |
| Genotype GA | 9 Participants | 9 Participants | 18 Participants |
| Genotype GG | 16 Participants | 14 Participants | 30 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 2 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 | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 19 Participants | 18 Participants | 37 Participants |
| Region of Enrollment United States | 25 participants | 23 participants | 48 participants |
| Sex: Female, Male Female | 16 Participants | 14 Participants | 30 Participants |
| Sex: Female, Male Male | 9 Participants | 9 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 30 |
| other Total, other adverse events | 9 / 30 | 15 / 30 |
| serious Total, serious adverse events | 1 / 30 | 0 / 30 |
Outcome results
Primary
Changes in Thalamic Standardized Uptake Value Ratio (SUVR)
The ratio of the standardized uptake value (SUV; mean radioactivity divided by the injected dose by weight) of the whole thalamus divided by the SUV of the whole brain (i.e., standardized uptake value ratio or SUVR) derived from the translocator protein positron emission tomography (TSPO-PET) signal. Higher SUVR might be indicative of higher neuroinflammation.
Time frame: The outcome measure was assessed in two time points, before and after a two-week treatment period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Minocycline Arm | Changes in Thalamic Standardized Uptake Value Ratio (SUVR) | - Pre-treatment Thalamic SUVR | 1.188 Standardized uptake value ratio | Standard Deviation 0.051 |
| Minocycline Arm | Changes in Thalamic Standardized Uptake Value Ratio (SUVR) | - Post-treatment Thalamic SUVR | 1.189 Standardized uptake value ratio | Standard Deviation 0.045 |
| Placebo Arm | Changes in Thalamic Standardized Uptake Value Ratio (SUVR) | - Pre-treatment Thalamic SUVR | 1.166 Standardized uptake value ratio | Standard Deviation 0.056 |
| Placebo Arm | Changes in Thalamic Standardized Uptake Value Ratio (SUVR) | - Post-treatment Thalamic SUVR | 1.165 Standardized uptake value ratio | Standard Deviation 0.054 |
p-value: 0.95695% CI: [-0.02, 0.02]Mixed Models Analysis
Secondary
Changes in Spinal PET Signal
The investigators will test for the presence of a significant treatment\*time interaction in the spinal \[11C\]PBR28 signal.
Time frame: 2 weeks
Secondary
Daily Pain Ratings (as Measured by the Modified Brief Pain Inventory (BPI) Severity Subscale)
The investigators will test for the presence of a significant treatment\*time interaction in pain outcomes using the severity subscale of the Brief Pain Intensity, short form (range 0-10)
Time frame: 2 weeks