Evaluating the Role of Neuroinflammation in Low Back Pain: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluating the Role of Neuroinflammation in Low Back Pain (NCT03106740), a randomized phase 2 study. The primary outcome is Changes in Thalamic Standardized Uptake Value Ratio (SUVR).

2. Clinical Question

The study also examined spinal PET signal and the rate of change in daily Modified Brief Pain Inventory (BPI) Severity Subscale scores as secondary outcomes. These outcomes address related but distinct questions: whether an imaging signal changes in the spinal region and how reported pain severity changes during the treatment period. The record describes evaluation of neuroinflammation in the brain and spinal cord, but the listed primary endpoint is specifically a thalamic-to-whole-brain PET signal ratio.

3. Trial Design

The IGNITE Study is a Phase 2 randomized, quadruple-masked, parallel-group trial. The registry records an enrollment of 60. It describes two arms: minocycline and placebo. The minocycline arm received a 100mg capsule during a two-week trial, while the placebo arm received a placebo capsule for two weeks. Imaging and/or behavioral pain assessments were planned before and after treatment.

The study start date is 2017-10-10, the primary completion date is 2024-04-30, and the status is completed. These are registry entries about the study timeline and status; they do not establish when all analyses were conducted or whether every enrolled participant contributed data to each outcome. Those details are not reported in the registry record.

Randomization is intended, in general, to reduce systematic differences between assigned groups, while masking is intended to limit the influence of treatment knowledge on participants, investigators, and outcome assessment. The record identifies the allocation as randomized and the masking as quadruple, but does not identify which groups of people were masked or describe the randomization procedure, allocation concealment, or implementation.

The parallel design means the arms are described as separate treatment groups rather than as a crossover sequence. The registry record does not report the protocol’s sample-size justification, planned statistical analysis, or whether the enrolled number differed from the planned enrollment. The posted safety figures list 30 at risk in each arm, but these figures alone do not describe the analysis population for the primary endpoint.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: 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.

6. Primary Endpoint

The registry lists the primary outcome as Changes in Thalamic Standardized Uptake Value Ratio (SUVR), measured over The outcome measure was assessed in two time points, before and after a two-week treatment period..

The primary endpoint is change in thalamic standardized uptake value ratio (SUVR). SUVR is defined in the registry as the standardized uptake value (SUV) for the whole thalamus divided by the SUV for the whole brain. The SUV is described as mean radioactivity divided by injected dose by weight. The signal comes from translocator protein positron emission tomography (TSPO-PET).

The endpoint was assessed before and after a two-week treatment period. It is a continuous imaging measure, and the registry specifies that the outcome is summarized as a mean with standard deviation. A ratio can provide a relative measure of the thalamic PET signal against the whole-brain signal. The registry states that higher SUVR might be indicative of higher neuroinflammation; this is a cautious interpretation of the imaging measure, not a direct count of inflammatory cells or a diagnosis.

Imaging makes this endpoint relevant to the study’s question about neuroinflammation in the brain. However, the primary measure concerns the thalamus relative to the whole brain; it should not be treated as a direct measure of all brain or spinal inflammation. The registry record does not report the observed means, standard deviations, change estimates, or a between-arm comparison. It therefore does not establish the direction, size, or precision of any treatment-associated change in SUVR.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry classifies the primary endpoint as a continuous outcome summarized by a mean and standard deviation. In general, a mean describes the center of a set of measurements, while a standard deviation describes how spread out individual measurements are around that mean. These summaries help characterize an arm’s measurements, but they do not by themselves quantify the uncertainty around a comparison between arms. The registry record does not report the endpoint’s observed means or standard deviations.

What does the primary measure represent?

Thalamic SUVR is a ratio of the whole-thalamus SUV to the whole-brain SUV, based on TSPO-PET signal. A ratio is a relative measure: its value depends on the signal in the numerator and denominator. In general, a difference in a ratio can reflect change in either component or both. The registry describes higher SUVR as potentially indicative of higher neuroinflammation. The record does not report the imaging data or methods needed to assess how changes in each component contributed to the outcome.

Why compare the arms rather than only changes within each arm?

In general, measurements made before and after treatment can be described as within-arm changes. A randomized comparison asks whether the change differs between the assigned treatment arms. That distinction matters because changes over time may occur for reasons other than the assigned treatment. A placebo arm offers a contemporaneous comparison, but the statistical estimate and its uncertainty are needed to interpret the contrast. The registry record does not report a single primary comparison, its estimate, or its uncertainty.

What does randomization contribute?

Random assignment is intended, in general, to make treatment groups comparable with respect to both measured and unmeasured characteristics at the point of assignment. It does not guarantee that the groups will be identical, particularly in a trial with limited enrollment, and it cannot correct for all later problems such as missing outcome data. The registry identifies the study as randomized but does not report the sequence-generation method, allocation concealment, or analysis approach.

How should uncertainty be read?

In general, a confidence interval gives a range of effect estimates compatible with the data and the assumptions of the analysis. Its width conveys precision: wider intervals indicate less precise estimates. A p-value addresses how compatible the observed data are with a specified null model under the analysis assumptions; it is not the probability that a treatment works or that the null hypothesis is true. Neither a confidence interval nor a p-value for the primary outcome is reported in the registry record, so no such inferential interpretation can be made from the posted primary outcome information.

What do the planning illustrations mean?

The study’s posted sample-size illustrations are described as planning calculations based on the observed effect, not as the trial’s own design justification. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. In general, such calculations show how a hypothetical future study’s size may vary with the target effect and desired power. They are not observed power, and they do not show that the completed trial was designed around those assumptions. The protocol’s sample-size justification is not reported in the registry record. The numerical planning outputs are not stated in the registry entries, so no participant requirement can be inferred from the assumptions alone.

For continuous outcomes, dispersion matters because greater variability makes a given contrast harder to estimate precisely. In general, a standard deviation helps describe that variability, while an analysis model determines how the outcome measurements are used to estimate an effect and its uncertainty. If data vary more than a model assumes, an analysis that fails to account for that over-dispersion can understate uncertainty. The registry does not report a model, an over-dispersion assessment, or a method for handling repeated measurements.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and secondary outcomes covering spinal PET signal and the rate of change in daily Modified Brief Pain Inventory (BPI) Severity Subscale scores. Examining multiple outcomes can raise a multiplicity issue: in general, the chance of at least one apparently notable finding can increase when many statistical tests are conducted. A prespecified hierarchy, adjustment procedure, or clear distinction between confirmatory and exploratory analyses can help readers interpret multiple tests. Such a plan is not reported in the registry record.

The primary outcome is described at before-and-after time points, but the registry does not reduce it to a single reported comparison. The statistical analysis plan, including the definition of the primary contrast and any multiplicity handling, is not reported in the registry record. The number and details of analyses for each outcome, beyond the registry’s recorded analysis count, are also not described.

Missing-data methods and outcome-specific analysis populations are not reported in the registry record. The enrollment figure and the safety at-risk counts do not establish how many participants had usable primary endpoint measurements, whether any measurements were missing, or how missing values were handled. The record also does not specify whether analyses were based on assigned treatment, treatment received, or another population definition.

In general, missingness can affect interpretation when the likelihood of an unavailable measurement is related to participant characteristics or outcomes. Methods such as complete-case analysis or imputation make different assumptions, and those assumptions should be stated to judge robustness. No particular missing-data method or sensitivity analysis can be attributed to this study from the registry record.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: stroke (3.3%).

The registry reports serious adverse events affecting 1 participant in the Minocycline Arm and 0 in the Placebo Arm. It lists 30 participants at risk for serious adverse events in each arm. These are counts from the registry’s safety record; they do not describe the primary imaging endpoint or establish a treatment effect. The registry also reports 0 deaths in each arm.

For other, non-serious adverse events, the record lists 9 affected participants in the Minocycline Arm and 15 in the Placebo Arm, with 30 at risk in each arm. These are affected-participant counts, not a complete description of event severity, duration, or clinical importance. The record does not report detailed event-level information or an analysis adjusting for differences in observation time.

Stroke is listed among the top serious adverse event terms at 3.3%. The registry record does not specify the arm associated with that term in the listed summary, so it should not be assigned to either arm on that basis. Counts in a trial of this size are descriptive and can be imprecise; they should not be treated as proof that a treatment causes or prevents an event. The record does not report a formal comparative safety analysis.

12. What the Result Does, and Does Not, Mean

The registry record establishes that the completed IGNITE Study was designed to compare minocycline with placebo in a randomized, quadruple-masked, parallel-group trial. Its primary outcome was change in thalamic SUVR, an imaging ratio derived from TSPO-PET and assessed before and after a two-week treatment period. The study also listed spinal PET signal and daily pain severity change as secondary outcomes.

What the posted results do not establish is the observed magnitude or direction of the primary outcome change. No group-level SUVR summaries, between-arm estimate, confidence interval, or p-value are reported in the registry record. Without those results, the data presented do not support a conclusion about whether the arms differed on the primary endpoint, or how precisely any difference was estimated. The existence of an imaging endpoint and a randomized comparison is not itself evidence of a particular result.

The endpoint is an imaging measure that the registry says might indicate neuroinflammation at higher values. It is not a direct measure of symptoms, function, or every aspect of inflammation in the brain and spinal cord. The separately listed pain outcome would need its own reported result and analysis to address change in pain severity. The record’s summary of study aims should not be substituted for outcome estimates.

The safety counts offer a limited descriptive account of adverse events and deaths. They do not establish the comparative safety of treatment, and they do not answer whether imaging or pain outcomes differed. Overall, the registry record provides study design, outcome definitions, and selected safety counts, but not the efficacy estimates needed to interpret the primary research question. Details of the analysis population, missing-data handling, and statistical plan are also not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable for linking a mechanistic imaging question with a randomized treatment comparison. Its primary outcome is not a symptom score but a PET-derived thalamic-to-whole-brain ratio. That distinction matters: the imaging measure addresses a biological hypothesis, while the separately listed daily pain outcome addresses reported symptom severity. Evidence on one measure cannot automatically answer questions about the other.

The before-and-after assessments create an important design issue. In general, observing change within a treatment arm is not equivalent to estimating a treatment effect. A randomized comparison needs to distinguish change associated with treatment assignment from change that might also occur in the placebo arm. The registry identifies the trial’s randomized structure but does not report the contrast or its statistical uncertainty.

The study also illustrates why endpoint definitions and inferential reporting both matter. The registry explains how SUVR is formed and how higher values might relate to neuroinflammation, but biological interpretation depends on the observed data and the analysis. Without numerical endpoint results, readers cannot judge the size, precision, or direction of the primary comparison.

Finally, the record lists multiple imaging and pain outcomes, while the multiplicity strategy and missing-data methods are not reported. Those details are important when interpreting a set of outcomes and assessing how robust conclusions may be. The trial’s statistical contribution can therefore be described in terms of its question and design, but the registry information does not support a conclusion about the primary treatment effect.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main trial-specific limitation of the posted record is that it describes the primary outcome but does not report its numerical results or a single comparison between arms. The primary endpoint covers measurements before and after treatment, yet the registry does not state a change estimate, group summaries, standard errors, confidence interval, or p-value. This prevents assessment of effect magnitude and precision.

The record describes the endpoint as a thalamic-to-whole-brain PET ratio and says higher SUVR might indicate higher neuroinflammation. It does not report details on imaging acquisition, processing, measurement reliability, or how the ratio’s components behaved. These omissions limit interpretation of the biological meaning of a change in the ratio. The record also does not report numerical results for the listed spinal PET or pain outcomes.

Further limitations arise because the analysis population, missing-data handling, and statistical model are not reported in the registry record. The method of randomization and the people included under quadruple masking are not described. The protocol’s sample-size justification and planned multiplicity approach are also not reported. These are not details that can be inferred from the completed status or from the arm descriptions.

The safety summary provides counts but limited context about event timing, duration, severity beyond the serious/non-serious distinction, and arm-specific serious-event terms. No formal comparative safety analysis is reported. These points restrict the conclusions that can be drawn from the registry record; they do not establish that the trial lacked such analyses or procedures outside the information recorded there.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Evaluating the Role of Neuroinflammation in Low Back Pain — NCT03106740.
• Registry record last updated 2026-02-11; status last verified 2026-01.
• Results first posted 2025-05-11.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The IGNITE Study, registered as NCT03106740, is recorded as a completed Phase 2 randomized, quadruple-masked, parallel-group trial with enrollment of 60. It compared a two-week course of minocycline hydrochloride 100mg capsule with placebo in people with low back pain. The primary outcome was change in thalamic SUVR from TSPO-PET, assessed before and after treatment. Secondary outcomes included changes in spinal PET signal and daily Modified Brief Pain Inventory Severity Subscale scores.

The registry lists adverse-event counts and deaths by arm, but does not report numerical results for the primary endpoint or a single between-arm comparison. The analysis plan, analysis population, missing-data methods, and multiplicity strategy are not reported in the registry record.