Resting-State Neural Connectivity in Patients With Subjective Tinnitus Without Bother: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Resting-State Neural Connectivity in Patients With Subjective Tinnitus Without Bother (NCT01049828), a registered phase not stated study. The primary outcome is Number of Participants With Changes in Blood Oxygen Level as Measured by Functional Connectivity MRI.

2. Clinical Question

The study’s stated rationale is that bothersome tinnitus has been associated in earlier work described in the registry with changes in attention and control networks, alongside concentration and focus difficulties. The question for this study is narrower: whether people who experience tinnitus without substantial bother also show connectivity patterns of interest. The record describes the intended imaging and comparison, but it does not report the measured connectivity findings or a statistical estimate of a difference between groups. It therefore cannot establish from the registry record whether the proposed patterns were present, how large any group difference was, or how precisely it was estimated.

3. Trial Design

This is a completed study sponsored by Washington University School of Medicine. The registry lists a start date of 2010-08 and primary completion in 2012-05, with enrollment of 20 participants. The listed intervention is No intervention, classified as OTHER. The described activity is functional connectivity MRI in participants with tinnitus that was not bothersome or was only slightly bothersome.

The study was not described as a randomized comparison. Its stated aim was to recruit or identify a non-bothered tinnitus group matched on age and hearing status to an existing cohort of bothered tinnitus patients. The record says the control group was collected through a different study and that no controls would be recruited for this study. The record does not establish that matching was achieved, nor does it give the comparator cohort’s size, participant characteristics, or imaging results. Consequently, the design description indicates an intended comparison rather than a documented, like-for-like control comparison in the enrolled study.

Eligibility is described using a subjective rating of no or slight bother and a Tinnitus Handicap Index threshold. The group description specifies a score <36, whereas the primary-outcome population description specifies less than 30. The registry does not explain this difference. It is therefore not possible to identify from the record which threshold governed every participant’s eligibility or the primary analysis population.

The registry lists enrollment of 20, while the adverse-event record reports 19 participants at risk. These are different record entries, and the reason for the difference is not reported in the registry record. The study is marked COMPLETED, but completion status does not itself provide the outcome findings or clarify which participants contributed to each analysis. Further details about allocation, blinding, analysis populations, and the statistical analysis plan are not reported in the registry record.

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.

Before assignment: 1 participant was excluded due to claustrophobia from the MRI and another participant withdrew midway through the neurocognitive evaluation due to frustration.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Perform Functional Connectivity MRI on Participants With Non-bothersome Tinnitus. Non-Bothered Tinnitus Group includes participants who answer 'no bother' or 'slight bother' on a global tinnitus bothersome scale and less than 30 on the Tinnitus Handicap Index.

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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Changes in Blood Oxygen Level as Measured by Functional Connectivity MRI, measured over 8 months for complete analysis on all participants.

The primary outcome is titled as the number of participants with changes in blood oxygen level measured by functional connectivity MRI. The accompanying description says MRI is used to delineate networks associated with tinnitus, including default mode, attention, auditory, visual, somatosensory, and cognitive networks. Functional connectivity differences are described as measured through changes in blood oxygen level.

Imaging measures are used to characterize patterns of connectivity between brain regions or networks rather than to record a participant’s subjective description alone. In general, blood oxygen level changes provide an indirect imaging signal used in functional MRI to study brain activity and connectivity. That general role does not mean that a particular change is inherently beneficial or harmful, or that it identifies a cause of tinnitus.

The registry’s endpoint title frames the outcome as a participant count, but it does not state a rule for what qualifies as a change, a threshold for classifying a participant, or a specific summary of connectivity differences. The timeframe is described as 8 months for complete analysis on all participants. The posted record does not report the number of participants meeting an endpoint definition, the imaging values, or a comparison estimate. Without an operational definition and reported outcome data, the endpoint’s direction and magnitude cannot be interpreted from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a brain-imaging question, not a treatment comparison. Participants with tinnitus characterized as no or slight bother were to undergo functional connectivity MRI. The scientific aim was to assess resting-state neural connectivity and relate the findings to an existing cohort described as having bothersome tinnitus. Since no intervention is listed, treatment-effect language would not fit the stated design. The relevant statistical target would be a description of imaging measures in the study group and, if a comparator analysis was conducted, a comparison between groups.

What a group comparison would require

In general, comparing two groups requires a clearly defined measure for each participant, a defined analysis population, and a statistical summary of the difference. If groups differ in age, hearing status, or other characteristics related to the imaging measure, those differences may complicate interpretation. The study description says age and hearing status were intended matching factors, but the registry does not report whether matching was completed or how the comparison was analyzed. It also does not identify a specific comparator analysis in the posted results.

Here, the proposed comparator was drawn from an existing cohort, with the registry noting that the control group came from a different study. In general, using previously collected participants can make group comparability important: participant selection, procedures, and measurement conditions may not be identical across studies. The record does not report enough information to evaluate those features. It would be inappropriate to assume that matching or other adjustment removed potential differences between the groups.

Reading an imaging endpoint

Functional MRI measures changes in blood oxygen level as an indirect signal. In general, functional connectivity analyses use patterns of this signal to characterize coordinated activity across brain areas or networks. The registry lists several networks of interest, but it does not provide a detailed imaging processing plan, specify the exact connectivity metric, or state how a participant would be classified as having a change. Those details matter because different measurement and classification choices can lead to different summaries.

The endpoint title refers to a number of participants with changes, while its description refers more broadly to connectivity differences measured by blood oxygen level changes. The registry does not resolve whether the planned primary analysis was a participant count, a continuous imaging measure, or another summary. Nor does it specify a threshold or direction for classifying a change. Without those details and the resulting data, the outcome cannot be reconstructed or independently interpreted from the registry record.

Uncertainty and statistical evidence

In general, an estimate describes the size and direction of a measured quantity, while a confidence interval conveys uncertainty around that estimate. A statistical test can assess how compatible observed data are with a specified null hypothesis under stated assumptions. Neither an estimate, interval, nor primary-outcome test result is reported in the registry record. Thus, no conclusion about statistical evidence or precision is available for the connectivity question.

For binary outcomes, event counts are interpreted alongside the number of participants assessed. A count without its analysis denominator is incomplete, and a denominator alone does not show the frequency of an outcome. The registry’s primary endpoint is presented as a participant count, but its observed count and analysis denominator are not reported. The safety entries are separate and cannot serve as a substitute for the primary connectivity outcome.

Planning calculations are not study findings

General sample-size planning illustrations can show how a hypothetical future study’s required size changes with assumptions about the effect to detect, significance level, allocation, and statistical model. The planning assumptions associated with this record use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the illustration is based on a stated fraction of an observed effect. Those are planning assumptions, not evidence that the study was designed or analyzed that way. The registry does not report the trial’s own sample-size justification or statistical analysis plan, and the observed effect value needed to assess the illustration is not reported in the registry record.

Such calculations should not be described as observed power. In general, power is a design concept tied to assumptions about an effect and variability, whereas results are interpreted through estimates and their uncertainty. A planning illustration cannot compensate for missing outcome data, verify that the analysis followed its assumptions, or establish that the completed study could detect a particular difference.

Counts and dispersion

The outcome is identified as binary and as a count of participants with an event. General methods for count outcomes depend on how events are defined and whether participants can contribute more than one event. Over-dispersion matters when observed count variability exceeds what a chosen count model assumes; in that situation, standard errors from the simpler model may understate uncertainty. The record does not report repeated events, an over-dispersion assessment, or a count model, so no such method can be attributed to this study. The central methodological limitation is that the registry lacks the observed primary data and analysis details needed to assess which statistical methods, if any, were used.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Non-Bothered Tinnitus Group")
n      <- c(18)
events <- c(18)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Non-Bothered Tinnitus Group  18  18  100.0  81.5  100.0  82.4  100.0  82.4  99.9

11. Multiplicity, Missing Data and Analysis Populations

The registry describes several networks of interest: default mode, attention, auditory, visual, somatosensory, and cognitive. It does not report whether each network was a separate endpoint, whether one was designated as primary for statistical testing, or how multiple comparisons were handled. When many outcomes or hypotheses are tested, general statistical practice considers multiplicity because repeated testing can increase the chance of at least one apparently notable result. No multiplicity adjustment or hierarchy of tests is reported in the registry record, so the impact of multiple analyses cannot be assessed.

Missing-data methods are also not reported in the registry record. There is no account of imaging failures, incomplete scans, participant withdrawals, or the handling of missing measurements. Enrollment is listed as 20, while 19 participants are listed at risk in the safety record; the reason for that difference is not stated. These entries do not identify the primary analysis denominator or demonstrate that missing outcome data occurred, so neither should be inferred from them.

The record does not describe an intention-to-treat population, a per-protocol population, or another analysis set. Since no intervention is listed, conventional treatment-trial analysis labels may not apply, but the registry still would need to define which participants and measurements contributed to the endpoint analysis. That information, along with imputation or exclusion rules, is not reported in the registry record. As a result, the completeness and population basis of any primary analysis cannot be evaluated from the posted results.

12. Safety Results

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

Other (non-serious) adverse events

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

The safety record lists 19 participants at risk in the Non-Bothered Tinnitus Group. It reports 0 serious adverse events and 0 other adverse events for that group. These are the recorded event counts, not evidence that every participant was free of symptoms or that every possible event was assessed. The registry provides no serious adverse-event terms in its list of leading terms.

Deaths are recorded as null rather than as a numeric count, so the death count is not reported in the registry record. The safety denominator of 19 is separate from the enrollment entry of 20. The record does not explain the difference, and the safety denominator should not be treated as the primary imaging analysis denominator.

In general, adverse-event counts are interpreted in context: the number of participants monitored, the event definitions, the observation period, and the completeness of reporting all matter. The registry does not give a safety observation timeframe or detailed event collection methods. These figures therefore describe only the safety entries recorded for the listed group; they do not establish broader safety conclusions.

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

The record establishes that a completed study was registered to assess resting-state functional connectivity in people with tinnitus described as not bothersome or slightly bothersome. It identifies blood oxygen level changes measured with functional connectivity MRI as the basis for assessing networks relevant to tinnitus. It also states an intended scientific comparison with a previously collected group of people with bothersome tinnitus.

What the record does not provide is the primary endpoint result. There is no reported participant count for the stated outcome, no connectivity measurement, and no estimate comparing the non-bothered group with the existing cohort. Without those results, it is not possible to say whether the groups differed, whether any difference was precise, or whether the hypothesized attention and control network patterns were observed. A completed status does not fill this gap.

The record also does not show that any connectivity pattern caused tinnitus bother, concentration difficulty, or another experience. In general, an association between an imaging measure and a participant group does not by itself establish causation. Interpretation would depend on a prespecified measure, clear group definitions, participant comparability, analysis methods, and uncertainty estimates. Those details are not available in the posted results.

The most defensible reading is therefore limited: the study had an imaging objective and a described non-bothered tinnitus group, but the registry record does not report the findings required to answer its main question. The absence of reported primary results is not evidence that a difference was absent, nor is it evidence that a difference was present. It leaves the direction, magnitude, and statistical uncertainty of the proposed comparison unknown.

14. Why This Trial Matters Statistically

This study addresses a distinction that is important for statistical interpretation: experiencing tinnitus and being bothered by tinnitus are not identical descriptions of a study population. By focusing on participants characterized as having no or slight bother, the stated aim was to examine whether resting-state connectivity patterns could also be characterized in a group outside the bothered cohort. That framing raises a question about how symptom experience relates to imaging measurements, rather than a question about the effect of an assigned treatment.

The registry also makes the comparison structure consequential. The non-bothered group was to be compared with a cohort collected through a different study, and the record describes age and hearing-status matching as an aim. In general, comparisons across separately assembled groups require careful definition of eligibility, measurement procedures, and analysis populations. A result can be difficult to interpret if those features are not documented, even when the scientific question is well motivated.

Statistically, the record illustrates why an endpoint description is not a substitute for an endpoint result. A list of networks and an imaging measure explain what researchers intended to study, but they do not reveal an effect estimate, its uncertainty, or the extent of missing data. Since the primary results and analysis details are not reported in the registry record, readers cannot assess whether the evidence supported the proposed comparison or how precisely it did so.

The study remains informative about the intended research question and the broad measurement approach, while its posted statistical evidence is limited. Keeping those two things distinct prevents the rationale and completion status from being mistaken for a finding.

15. 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 limitation for interpreting this study is the absence of reported primary outcome values. The registry gives an outcome title and measurement description but no observed participant count, imaging summary, between-group estimate, confidence interval, or test result. Consequently, the central question cannot be answered from the posted results.

The population definition is not fully consistent across the record: the group description uses a Tinnitus Handicap Index threshold of <36, while the primary-outcome population description uses less than 30. The record does not explain which threshold was applied or whether the descriptions refer to distinct eligibility steps. The subjective bother criterion is described, but the registry does not give further detail on its administration.

The comparator information is also limited. The study planned to draw on a previously collected cohort, and the record says no controls would be recruited in this study. The comparator’s size and characteristics, the degree to which age and hearing status were matched, and the comparability of imaging procedures are not reported in the registry record. Because the comparison was not randomized, any group contrast would require careful consideration of potential differences between cohorts.

Additional analysis details are not reported, including the exact connectivity metric, operational definition of a participant-level change, analysis population, missing-data handling, multiplicity approach, and statistical analysis plan. Enrollment of 20 and the safety denominator of 19 are distinct record entries whose discrepancy is unexplained. Together, these limitations prevent assessment of the primary analysis’s completeness, precision, and robustness.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Resting-State Neural Connectivity in Patients With Subjective Tinnitus Without Bother — NCT01049828.
• Registry record last updated 2024-07-25; status last verified 2024-02.
• Results first posted 2024-07-25.
• 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.

19. Record Summary

NCT01049828 is a completed study sponsored by Washington University School of Medicine, with enrollment listed as 20. It was registered to assess resting-state neural connectivity in people with subjective tinnitus characterized as not or slightly bothersome, using functional connectivity MRI and blood oxygen level changes. The intended comparison involved an existing bothered tinnitus cohort; no control group was to be recruited within this study.

The record describes one primary outcome, titled as the number of participants with changes in blood oxygen level, and a timeframe of 8 months for complete analysis on all participants. It does not report the observed primary outcome or the statistical results. The listed safety group has 19 participants at risk, with 0 serious adverse events and 0 other adverse events; deaths are not reported as a numeric count. Key details about the comparator, analysis population, missing data, multiplicity, and statistical methods are not reported in the registry record.