Neurotropin to Treat Chronic Neuropathic Pain: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Neurotropin to Treat Chronic Neuropathic Pain (NCT00006289), a randomized phase 2 study. The primary outcome is Visual Analogue Scale (VAS) of Pain Scores After Administration of Test Drugs (Placebo or Neurotropin ).

2. Clinical Question

The clinical question is framed around chronic neuropathic pain associated with complex regional pain syndrome. The registry describes type I as pain after a relatively minor injury that persists longer and is more severe than expected, and type II as pain resulting from injury to a large nerve. Its official title also mentions acute dental pain, but the posted primary outcome description concerns pain scores after the placebo and Neurotropin intervals in the crossover study. The registry record does not explain that difference in titles.

The treatment comparison is not a simple parallel-group comparison in which each participant receives only one assigned treatment. Participants crossed from one treatment to the other, so scores relate to both treatment and the order and period in which treatment was received. That design makes questions about period effects, carryover, and within-person comparisons important when interpreting the results. The registry does not report whether those effects were assessed.

3. Trial Design

The registry identifies this as a Phase 2, randomized, quadruple-masked, crossover study. It lists an enrollment of 21 and a terminated status. The recorded start is 2000-09, and primary completion is recorded as 2012-06. These registry entries describe the trial record; they do not establish how many participants completed both treatment periods or were included in the posted outcome analysis.

Two randomized treatment sequences are described. One began with placebo for 5 weeks and then switched to Neurotropin for 5 weeks. The other began with Neurotropin and then switched to placebo for 5 weeks. Both sequences included at least 1 week without trial medicine between the treatment intervals. The assignment was described as being selected by the pharmacy, with others blind to it. The registry’s overall masking designation is quadruple, while the sequence descriptions use the phrase double blind; which roles were masked is not reported in the registry record.

The study description says participants with complex regional pain syndrome type I or type II would receive an individualized physical-therapy regimen and standard treatment for pain in addition to the trial medicine. Thus the posted treatment comparison sits alongside those other care elements rather than representing Neurotropin versus no care.

The registry describes a planned target of 30 participants in the primary outcome text and says an interim analysis would be performed after the first 16 participants if recruitment was difficult. It also says the analysis of those 16 participants was conducted while investigators were blinded to the treatment code, with unblinding after analysis. The posted record does not state whether that interim analysis occurred, what decisions it informed, or whether the stated target changed. The registry’s enrollment entry is 21; the record does not explain the difference between that enrollment and the planned target.

The primary outcome is a mean pain score after each 5-week treatment interval. Although the design is crossover, the posted values are separated by treatment sequence and period. The registry does not report participant-level paired results or a crossover model that would clarify how within-person dependence and treatment order entered the analysis.

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: Patients who have abnormal results from routine laboratory test or are positive for HIV are excluded. Women who are pregnant or positive for pregnancy test are excluded. Also patients who have non-traumatic pain disorders or are obviously have impaired mental capacity are excluded.

First Intervention (5 Weeks)

Reasons for not completing this period:

Washout (>= 1 Week)

Second Intervention (5 Weeks)

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: Clinical evaluation includes blood chemistries (acute care, hepatic panel, and mineral panel) as well as measurements of pain (including allodynia, hyperalgesia, and hyperpathia), edema, autonomic dysfunction (altered skin color, temperature, or sudomotor activity) and extent of movement disorders.

6. Primary Endpoint

The registry lists the primary outcome as Visual Analogue Scale (VAS) of Pain Scores After Administration of Test Drugs (Placebo or Neurotropin ), measured over VAS of each patient is measured after each 5-week treatment interval with placebo or Neurotropin..

The primary endpoint is the patient-rated Visual Analogue Scale (VAS) of pain after each treatment interval. The scale ranges from 0 to 100 mm, with 0 defined as no pain and 100 as the maximal pain level. A patient marks a position on the scale to express perceived pain severity, producing a continuous measurement rather than a count or category.

Pain intensity is relevant to the study’s stated question because the trial investigates treatment for chronic pain after limb or large-nerve injury. A patient-reported measure can capture the participant’s own assessment of pain, rather than relying only on an external observer. The registry does not report information about the scale’s measurement properties in this study, how the mark was collected, or whether participants received standardized instructions beyond the scale endpoints.

The recorded timeframe is measurement after each 5-week treatment interval. The posted mean and standard error are grouped by sequence and period: placebo first and Neurotropin second, or Neurotropin first and placebo second. Because each sequence includes both treatments, the values need to be read in the context of crossover order, not as independent parallel treatment arms. The registry does not report an overall treatment-specific mean, a paired mean difference, or a confidence interval for a treatment contrast.

For a continuous endpoint, the mean describes the average score in the reported group, while the standard error describes the uncertainty in that estimated mean. It is not a measure of the range of individual pain scores. The registry does not post standard deviations or individual-level data from which the distribution of participant scores could be inspected.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical features matter when reading the posted outcome: the crossover structure, the continuous scale, the reported group summaries, and the one-sided test. The registry supplies some descriptive information but does not report the full analysis plan or enough detail to reconstruct a treatment contrast.

What does a crossover design compare?

In a crossover design, participants receive more than one treatment in a defined order. Here, one sequence received placebo and then Neurotropin; the other received Neurotropin and then placebo. A participant’s results under the two treatments are therefore related observations. A treatment comparison can use that within-person pairing, which may be informative because stable characteristics of a participant are shared across their treatment periods.

That benefit depends on appropriate analysis and on the assumptions being reasonable. A crossover analysis must consider whether outcomes change over time regardless of treatment, whether treatment effects depend on order, and whether effects from the first treatment persist into the next period. The registry describes a washout of at least 1 week but does not report an assessment of carryover or period effects. The reported one-sided t-test is not described as a paired test or as a crossover model, so its handling of these features is not reported in the registry record.

What do the means and standard errors describe?

A mean is the arithmetic average of the observed scores in a group. The four posted means summarize pain scores for each treatment within each sequence and period. They are useful descriptive values, but their interpretation depends on the group definition. In particular, the placebo-first sequence’s placebo-period mean and Neurotropin-period mean come from the same sequence of participants, while the other two means come from the opposite sequence.

A standard error describes the sampling uncertainty of an estimated mean. It is not the spread of individual scores and does not show how much participants varied from one another. A confidence interval would give a range of values compatible with the data and analysis assumptions, but no confidence interval for a treatment contrast is reported. Separate standard errors for the four means cannot reveal the within-participant correlation needed to reconstruct a paired comparison.

How should the reported test be read?

The registry identifies a one-sided t-test and reports p = 0.006. A t-test evaluates a specified hypothesis about means under assumptions appropriate to the design and data. A one-sided test addresses a directional alternative, rather than departures in either direction. The registry record does not specify the directional alternative, test statistic, degrees of freedom, or the exact contrast tested. It also does not clarify whether the test treated the four sequence-period groups jointly or how participant pairing was handled.

A p-value measures how incompatible the observed data are with a particular null hypothesis under the test’s assumptions. It is not the probability that the null hypothesis is true, and it does not quantify the size or clinical importance of a difference. Because the exact null hypothesis is not stated, even that statistical interpretation must remain tied to the registry’s limited description.

Why does over-dispersion matter for count data?

General statistical explanation: over-dispersion occurs when count outcomes vary more than a model assumes. It can make standard errors too small if the extra variability is ignored. This consideration does not define the primary outcome in this trial: pain is measured on a continuous VAS, not as a count. The registry does not report a count-based primary analysis.

What do planning calculations mean?

General statistical explanation: a sample-size calculation describes how many participants a design might require under stated assumptions about an effect, variability, significance level, and allocation. It is a planning illustration, not an observed property of the completed trial and not a measure of the probability that a result is true. The registry’s planning assumptions describe a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects defined as fractions of the observed effect. Specific planning counts are not reported in the registry record, and the posted record does not give the trial’s own sample-size justification.

These distinctions are especially important for a small crossover study with incomplete reporting. The registry reports group means, standard errors, group counts, and a one-sided p-value, but not a paired treatment estimate, its confidence interval, the analysis population, or a complete statistical model. The available summaries therefore support description of the recorded scores, but not an independent reconstruction of the intended treatment-effect analysis.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("VAS After Placebo Treatment First in G-1", "VAS After Neurotropin Treatment Second in G-1", "VAS After Neurotropin Treatment First in G-2", "VAS After Placebo Treatment Second in G-2")
n   <- c(7, 7, 9, 9)
m   <- c(33.6, 38.3, 36, 31.1)
sp  <- c(11.1, 8.8, 7.6, 7.7)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  VAS After Placebo Treatment First in G-1  7  33.600  29.368  6.439  60.761
CARM  VAS After Neurotropin Treatment Second in G-1  7  38.300  23.283  16.767  59.833
CARM  VAS After Neurotropin Treatment First in G-2  9  36.000  22.800  18.474  53.526
CARM  VAS After Placebo Treatment Second in G-2  9  31.100  23.100  13.344  48.856

11. Analyses Reported by the Sponsor

The registry reports the sponsor’s own analysis as a one-sided t-test with p = 0.006. It does not provide the estimated contrast, a confidence interval, or enough detail to identify exactly which comparison that test represents. The record does not include a separately reproducible treatment comparison from the posted summary statistics: the four groups are sequence-period summaries, and the paired participant-level information needed for a crossover re-calculation is not reported.

There is therefore no recalculated treatment estimate to set beside the sponsor-reported result. The posted means and standard errors alone do not determine a valid paired treatment contrast, because they do not show the covariance between measurements from the same participants. The sponsor’s reported analysis remains the only inferential test in the registry record, but its interpretation is constrained by the missing contrast definition and analysis details.

The registry does not identify whether the displayed outcome results come from the interim analysis described in the outcome text or from a later analysis. It also does not state whether the reported p-value reflects any adjustment for interim monitoring. Consequently, the available record does not support a more detailed comparison between sponsor analysis and a re-analysis.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures and three analyses, but it does not provide details about a multiplicity strategy. It is not reported whether the primary pain outcome was the only confirmatory outcome, whether the other analyses were considered secondary or exploratory, or whether the one-sided p-value was adjusted for testing across outcomes or analyses. Without a prespecified testing hierarchy or adjustment description, the implications of multiple testing cannot be assessed from the registry record.

The primary outcome description also refers to an interim analysis after the first 16 patients if recruitment was difficult. It says the analysis was performed while investigators were blinded to treatment codes and that unblinding took place after the analysis was complete. The record does not state whether this interim analysis occurred, whether it was used for a decision, or how it was incorporated into the final statistical inference. It does not report a stopping boundary, an alpha-spending approach, or any other method for accounting for interim analysis. Those details are not reported in the registry record.

The registry’s enrollment entry is 21, while the outcome description refers to a target number of 30. The posted record does not explain the recruitment outcome, the number completing each interval, or the number included in the analysis. The group counts accompanying the outcome are presented by sequence and treatment period, but the record does not define the analysis population or state how missing outcome measurements were handled.

Missing-data methods are not reported in the registry record. It is not stated whether participants with incomplete crossover data were excluded, whether available-period observations were used, or whether any imputation was performed. The reasons for missingness and the completeness of measurements in each period are also not reported. In a crossover design, incomplete paired observations can affect which participants contribute to a treatment comparison, so these omissions matter for interpreting the means and test.

The record does not report whether analyses followed an intention-to-treat, per-protocol, or other population definition. These gaps prevent assessment of how exclusions, missing outcomes, interim monitoring, and multiple testing may have influenced the reported result.

13. 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 4% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports no participants with serious adverse events among those at risk in either sequence: 0 of 11 in the placebo-first-then-Neurotropin group, and 0 of 10 in the Neurotropin-first-then-placebo group. These figures are counts of participants affected, not counts of event episodes. The registry lists no serious adverse event terms.

For other adverse events, the registry reports 1 of 11 affected in the placebo-first-then-Neurotropin sequence and 0 of 10 in the Neurotropin-first-then-placebo sequence. These are sequence-level figures. Because participants crossed between treatments, the registry’s summary does not attribute these events to a particular treatment period. The figures should not be read as a direct treatment-specific comparison.

Deaths are recorded as null rather than as a count. The death information is therefore not reported in the registry record. The posted safety counts also do not describe event severity beyond the serious-versus-other categorization, timing, duration, or relationship to study treatment. With the information available, the counts describe what the registry recorded but do not establish comparative safety or the absence of unreported events.

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

The registry record documents a randomized crossover study of Neurotropin and placebo in participants with complex regional pain syndrome type I or type II. It reports patient-rated pain scores after each 5-week treatment interval, with a mean and standard error for each treatment sequence and period. It also reports a one-sided t-test with p = 0.006. These are the main statistical details available for interpreting the primary outcome.

The posted summaries do not report a treatment-specific contrast estimate or confidence interval. The exact contrast tested by the reported p-value is not specified, and the record does not describe how the crossover pairing, period, or possible carryover was handled. For these reasons, the reported test cannot be translated into a clearly defined estimate of the Neurotropin-versus-placebo difference from the registry record alone.

A statistically reported p-value does not by itself indicate the magnitude of a difference, its precision, or whether it is important to patients. The sequence-period means describe the observed scores in those groups, but they are not independent parallel-arm estimates. Nor do they show how much each participant’s score changed between treatments. The registry does not report individual data or a paired analysis that would answer that question.

The record also does not establish whether the interim analysis described in the outcome text occurred or whether the displayed results are interim or final. The enrollment entry and the planned target differ, and the record does not explain participant completion, missing outcomes, or the analysis population. Those uncertainties further limit interpretation.

Accordingly, the posted information supports a cautious description of the trial’s reported summaries and test, not a definitive estimate of treatment effect. It neither establishes that Neurotropin does or does not work nor provides a basis for medical advice. The registry record lacks the analysis detail and precision estimates needed to judge the size and reliability of a treatment comparison.

15. Why This Trial Matters Statistically

This trial illustrates why design details are essential to reading clinical results. A crossover study exposes participants to both treatments, so a treatment comparison is connected to within-person measurements, treatment order, and time. Reporting separate means by sequence and period is informative descriptively, but it does not replace a clearly specified paired treatment estimate.

It also shows the limits of interpreting a p-value without its contrast. A one-sided t-test is reported, but the registry does not identify the exact hypothesis or explain how the test accounts for the crossover structure. The p-value can therefore be quoted accurately while remaining cautious about what it represents. A confidence interval and a defined contrast would make the effect’s direction, size, and precision easier to assess.

The record’s reference to an interim analysis raises another important reporting issue. Knowing that an analysis was described is not enough to determine how it affected inference; the record would also need to clarify whether it occurred and how any interim monitoring was handled. Similarly, the enrollment entry, planned target, group counts, and incomplete reporting on missing outcomes leave the analysis population uncertain.

Finally, the safety figures are presented by sequence even though participants received both treatments. Such summaries should not be mistaken for treatment-specific event rates. Together, these features make the trial a useful example of how registry results can offer meaningful descriptive information while still leaving important questions about estimands, analysis, missingness, and precision unresolved.

16. 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 most important limitation for interpretation is incomplete statistical reporting. The registry gives a one-sided t-test p-value but does not state the exact contrast, test statistic, degrees of freedom, or whether the test used the paired nature of the crossover data. No treatment contrast estimate or confidence interval is posted. The group means and standard errors cannot recover those quantities without information about the within-participant relationship between measurements.

The sequence-period presentation also leaves period and carryover effects unresolved. The record describes at least 1 week without trial medicine between treatment periods, but does not report whether that washout was considered adequate or whether carryover was assessed. It does not state whether a period effect or sequence effect was included in the analysis. The registry’s quadruple-masking designation and the arm descriptions’ double-blind wording are not reconciled, and the roles masked are not reported.

The record describes an interim analysis after the first 16 patients if recruitment was difficult, but does not say whether it occurred or how it affected the reported test. It lists an enrollment of 21 and a target of 30, without explaining the difference. Completion by treatment period, the number of complete crossover pairs, the analysis population, and missing-data handling are not reported.

The outcomes are reported as means and standard errors, without standard deviations or individual participant results. The record therefore does not show the distribution of scores or allow assessment of influential observations. Although three outcome measures and three analyses are listed, multiplicity handling is not reported. The status is terminated, but the registry does not explain the reason for termination or its relationship to recruitment, conduct, or results.

These limitations concern the registry information and do not establish that particular methods were or were not used outside the record. They do restrict what can be verified from the posted information.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Neurotropin to Treat Chronic Neuropathic Pain — NCT00006289.
• Registry record last updated 2017-08-22; status last verified 2017-08.
• Results first posted 2016-06-21.
• 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.

20. Record Summary

This Phase 2 trial is listed as randomized, quadruple-masked, and crossover, with an enrollment of 21 and a terminated status. Participants were assigned to receive 5 weeks of Neurotropin and 5 weeks of placebo in randomized order, with at least 1 week without trial medicine between periods. The recorded start is 2000-09, and primary completion is recorded as 2012-06.

The primary outcome is patient-rated pain on a 0-to-100 mm VAS after each treatment interval. The registry reports four sequence-period means with standard errors and a one-sided t-test result of p = 0.006. It does not report a defined treatment contrast, confidence interval, crossover analysis details, interim-analysis status, missing-data approach, or analysis population. Safety summaries list no serious adverse events in either sequence, while deaths are not reported.