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CompletedNCT03106740IGNITEUpdated Feb 11, 2026Results posted

Evaluating the Role of Neuroinflammation in Low Back Pain

A Phase 2 interventional study of Minocycline Hydrochloride 100mg Capsule and Magnetic Resonance-Positron Emission Tomography Imaging in Low Back Pain, Back Pain With Radiation and Back Pain Without Radiation, sponsored by Marco Loggia. Completed at 1 site in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-02-11.

Sponsored by Marco Loggia · Phase 2, Interventional, and Basic science

Phase
Phase 2
Study type
Interventional
Enrollment
60
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Low Back Pain
  • Back Pain With Radiation
  • Back Pain Without Radiation
  • Back Pain Lower Back Chronic
  • Back Ache
  • Pain, Chronic

Keywords

  • Microglia
  • Minocycline
  • Magnetic Resonance Imaging
  • Positron Emission Tomography
  • Pain
  • Astrocytes
  • Glia
  • Human
  • Back Pain
03

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts 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

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
04

Study design

Phase
Phase 2
Primary purpose
Basic science
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
60 participants (actual)

Study arms

  • Experimental
    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

    Drug: Minocycline Hydrochloride 100mg Capsule · Diagnostic Test: Magnetic Resonance-Positron Emission Tomography Imaging

  • Placebo comparator
    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.

    Diagnostic Test: Magnetic Resonance-Positron Emission Tomography Imaging · Other: Placebo Capsule

Interventions

  • DrugMinocycline Hydrochloride 100mg Capsule

    Minocycline 100mg will be administered by mouth daily for 2 weeks

    Also known as: Minocin, Solodyn, Dynacin, Myrac

  • 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

05

What researchers measure

Primary outcomes

  1. 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.

Secondary outcomes

  1. Changes in Spinal PET Signal

    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.

    Time frame: 2 weeks

  2. Rate of Change in Daily Modified Brief Pain Inventory (BPI) Severity Subscale

    Estimated Mean Rate of Change of BPI per Day, separately by Treatment Group (Minocycline vs. Placebo), measured as Slope of Change over Time

    Time frame: 2 weeks

06

Results

Posted May 11, 2025

Participant flow

Participant flow — Overall Study
MilestoneMinocycline ArmPlacebo Arm
Started3030
Completed2523
Not completed57
Withdrew: Lost to follow-up22
Withdrew: Withdrawal by subject24
Withdrew: Physician decision01
Withdrew: Partial data10

Outcome measures

PrimaryChanges 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.
Reported as:
Mean · Standardized uptake value ratio
Changes in Thalamic Standardized Uptake Value Ratio (SUVR)
Standardized uptake value ratioMinocycline ArmPlacebo Arm
- Pre-treatment Thalamic SUVR1.188 ± 0.0511.166 ± 0.056
- Post-treatment Thalamic SUVR1.189 ± 0.0451.165 ± 0.054
Statistical analysis
  • Minocycline Arm vs Placebo Arm · Mixed Models Analysis · p = 0.956 (The p-value corresponds to the group-by-time interaction analysis of the primary outcome measure.) · Restricted maximum likelihood: 0.00 · 95% CI -0.02 to 0.02Estimation parameter: Unstandardized partial regression coefficient (beta)
SecondaryChanges in Spinal PET Signal

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.

Time frame:
2 weeks

Results for this outcome have not been posted.

SecondaryRate of Change in Daily Modified Brief Pain Inventory (BPI) Severity Subscale

Estimated Mean Rate of Change of BPI per Day, separately by Treatment Group (Minocycline vs. Placebo), measured as Slope of Change over Time

Time frame:
2 weeks
Reported as:
Number · The Brief Pain Inventory score per day
Rate of Change in Daily Modified Brief Pain Inventory (BPI) Severity Subscale
The Brief Pain Inventory score per dayMinocycline ArmPlacebo Arm
Rate of Change in Daily Modified Brief Pain Inventory (BPI) Severity Subscale-0.04 (-0.08 to -0.026)-0.03 (-0.062 to -0.006)

Adverse events

Collected over Between 14 and 43 days from the pre-treatment scan.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Minocycline Arm0/30 (0%)1/30 (3.3%)9/30 (30%)
Placebo Arm0/30 (0%)0/30 (0%)15/30 (50%)
Most frequent serious events
Most frequent serious events
EventMinocycline ArmPlacebo Arm
StrokeNervous system disorders1/300/30
Most frequent other events
Most frequent other events
EventMinocycline ArmPlacebo Arm
EcchymosisInjury, poisoning and procedural complications4/306/30
DiscomfortInjury, poisoning and procedural complications4/303/30
Gastrointestinal discomfortGastrointestinal disorders0/303/30
COVID-19 infectionInfections and infestations3/301/30
ClaustrophobiaInjury, poisoning and procedural complications0/302/30
Vasovagal syncopeInjury, poisoning and procedural complications1/301/30
RashSkin and subcutaneous tissue disorders0/301/30
ShinglesInfections and infestations0/301/30
PainMusculoskeletal and connective tissue disorders0/301/30
Skin cancer removalNeoplasms benign, malignant and unspecified (incl cysts and polyps)1/300/30

Baseline characteristics

While 60 participants were randomized, 12 participants (5 in the minocycline arm and 7 in the placebo arm) did not complete the study, resulting in a final sample size of 48. Please see the Reasons Not Completed section of the Participant Flow table for more detailed information.

Age, Continuous
Age, Continuous(Years)Minocycline ArmPlacebo ArmTotal
Mean44.6 ± 16.949 ± 17.145.9 ± 16.1
Sex: Female, Male
Sex: Female, Male(Participants)Minocycline ArmPlacebo ArmTotal
Female161430
Male9918
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Minocycline ArmPlacebo ArmTotal
American Indian or Alaska Native000
Asian235
Native Hawaiian or Other Pacific Islander000
Black or African American213
White191837
More than one race112
Unknown or Not Reported101
Region of Enrollment
Region of Enrollment(participants)Minocycline ArmPlacebo ArmTotal
United States252348
Genotype
Genotype(Participants)Minocycline ArmPlacebo ArmTotal
GG161430
GA9918
07

Study locations

1 site
  • Massachusetts General Hospital
    Charlestown, Massachusetts 02129, United States
08

References and documents

Publications

  • Loggia ML, Chonde DB, Akeju O, Arabasz G, Catana C, Edwards RR, Hill E, Hsu S, Izquierdo-Garcia D, Ji RR, Riley M, Wasan AD, Zurcher NR, Albrecht DS, Vangel MG, Rosen BR, Napadow V, Hooker JM. Evidence for brain glial activation in chronic pain patients. Brain. 2015 Mar;138(Pt 3):604-15. doi: 10.1093/brain/awu377. Epub 2015 Jan 12. PubMed 25582579 ↗
  • Vanelderen P, Van Zundert J, Kozicz T, Puylaert M, De Vooght P, Mestrum R, Heylen R, Roubos E, Vissers K. Effect of minocycline on lumbar radicular neuropathic pain: a randomized, placebo-controlled, double-blind clinical trial with amitriptyline as a comparator. Anesthesiology. 2015 Feb;122(2):399-406. doi: 10.1097/ALN.0000000000000508. PubMed 25373391 ↗
  • Mohammadian M, Morrissey EJ, Knight PC, Brusaferri L, Kim M, Efthimiou N, Murphy JP, Alshelh Z, Grmek G, Schnieders JH, Chane CA, Sandstrom A, Catana C, Gilman JM, Locascio JJ, Edwards RR, Zhang Y, Napadow V, Loggia ML. Investigating the potential of minocycline in reducing brain inflammation in chronic low back pain: a randomized, placebo-controlled mechanistic clinical trial. Pain. 2025 Apr 9;166(9):2044-2053. doi: 10.1097/j.pain.0000000000003543. PubMed 40839604 ↗
  • Morrissey EJ, Alshelh Z, Knight PC, Saha A, Kim M, Torrado-Carvajal A, Zhang Y, Edwards RR, Pike C, Locascio JJ, Napadow V, Loggia ML. Assessing the potential anti-neuroinflammatory effect of minocycline in chronic low back pain: Protocol for a randomized, double-blind, placebo-controlled trial. Contemp Clin Trials. 2023 Mar;126:107087. doi: 10.1016/j.cct.2023.107087. Epub 2023 Jan 16. PubMed 36657520 ↗

Study documents

  • Protocol and statistical analysis plan · May 12, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

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Registry details

Key details

Study ID
NCT03106740
Lead sponsor
Marco Loggia
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
Responsible party
Marco Loggia (Associate Professor of Radiology and Anesthesiology, Massachusetts General Hospital) — Sponsor-investigator
First posted
Apr 10, 2017
Start date
Oct 10, 2017
Primary completion
Apr 30, 2024
Completion
Apr 30, 2024
Results posted
May 11, 2025
Last update
Feb 11, 2026

Study contacts

Marco L Loggia, PhD
principal investigator · Massachusetts General Hospital

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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