PACE
(2026)Objective
To evaluate whether repeated 30-minute high-concentration capsaicin topical system (HCCTS) treatments plus standard of care improve peripheral sensory function in patients with painful diabetic peripheral neuropathy (PDPN), particularly those with baseline sensory deficits.
Study Summary
• Analysis 2 (HCCTS n=88 vs SOC n=89, below-normal baseline): Significant improvements with HCCTS+SOC vs SOC alone in BSPE heat (p=0.009), sharp (p=0.048), vibration (p=0.008)
• Norfolk QOL-DN total score (p<0.001) and large-fiber subscale (p<0.001) significantly improved with HCCTS+SOC
• No significant between-group differences in BSPE cold, deep tendon reflexes, or Norfolk QOL-DN small-fiber subscale
Intervention
30-minute high-concentration capsaicin (8%) topical system (HCCTS; QUTENZA) applied to the feet plus standard of care, with retreatment permitted at ≥8-week intervals up to a maximum of 7 treatments over 12 months.
Inclusion Criteria
Adults ≥18 years with painful diabetic peripheral neuropathy due to Type 1 or Type 2 diabetes for at least 1 year; for Analysis 2, required below-normal sensory function across all modalities at baseline.
Study Design
Arms: 30-min HCCTS + SOC (n=156) vs 60-min HCCTS + SOC (n=157) vs SOC alone (n=155); Analysis 2 subset with below-normal baseline sensory function: 30-min HCCTS + SOC (n=88) vs SOC alone (n=89)
Patients per Arm: 30-min HCCTS+SOC: 156; 60-min HCCTS+SOC: 157; SOC alone: 155 (full PACE population, N=468)
Outcome
• BSPE significant improvements with HCCTS+SOC vs SOC: heat (p=0.009), sharp (p=0.048), vibration (p=0.008)
• Norfolk QOL-DN total score significantly improved (p<0.001) with HCCTS+SOC vs SOC alone
• Large-fiber subscale significantly improved (p<0.001) with HCCTS+SOC; no significant difference in small-fiber subscale
• Positive shifts in BSPE scores from baseline were more common than negative shifts across all five modalities
Bottom Line
In this post hoc analysis of PACE, repeated 30-minute HCCTS treatments plus standard of care improved peripheral sensory function over 12 months in patients with painful diabetic peripheral neuropathy and baseline sensory deficits, with significant improvements in BSPE heat, sharp, and vibration as well as Norfolk QOL-DN total and large-fiber subscale scores. If confirmed in dedicated trials, sensory improvements may reduce diabetic foot complications by restoring protective sensation.
Major Points
- Analysis 1 (n=156): Repeated 30-min HCCTS treatments led to shifts from below-normal to normal sensory function at Month 12 in 21.1% (heat), 26.4% (cold), 22.8% (sharp), 4.2% (vibration), and 9.8% (deep tendon reflex) of tests
- Positive shifts in BSPE scores from baseline were more common than negative shifts across all five sensory modalities (heat, cold, sharp, vibration, deep tendon reflex)
- Analysis 2 (n=177 with below-normal baseline sensory function): Significant improvements with HCCTS+SOC vs SOC alone in BSPE heat (p=0.009), sharp (p=0.048), and vibration (p=0.008)
- Norfolk QOL-DN total score significantly improved with HCCTS+SOC vs SOC alone (p<0.001)
- Norfolk QOL-DN large-fiber subscale significantly improved (p<0.001); no significant difference in small-fiber subscale
- No significant between-group differences in BSPE cold or deep tendon reflexes
- Suggests possible neuroregenerative effect of HCCTS, with potential to restore protective sensation and reduce diabetic foot complications if confirmed in dedicated trials
Study Design
- Study Type
- Post hoc analysis of Phase III, multinational, open-label, randomized, controlled 52-week safety study
- Randomization
- Yes
- Blinding
- Open-label for treatment; BSPE assessments blinded to treatment allocation
- Sample Size
- 468
- Follow-up
- 52 weeks (12 months)
- Centers
- 71
- Countries
- 11 European countries
Primary Outcome
Definition: Changes in sensory function over 12 months as assessed by Brief Sensory Pain Examination (BSPE) and Norfolk QOL-DN with repeated 30-min HCCTS treatments + SOC vs SOC alone among patients with below-normal baseline sensory function (Analysis 2)
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| SOC alone (n=89) | 30-min HCCTS + SOC (n=88) | - | BSPE heat p=0.009; sharp p=0.048; vibration p=0.008; Norfolk QOL-DN total p<0.001; large-fiber subscale p<0.001 |
Limitations & Criticisms
- Post hoc analysis — hypothesis-generating, not confirmatory
- Open-label study design (though BSPE assessments were blinded)
- Analysis 1 used LOCF imputation, which may bias results
- Sensory function changes assessed by bedside BSPE rather than quantitative sensory testing (QST) or intraepidermal nerve fiber density (IENFD) measures
- No statistical testing in Analysis 1 (descriptive only)
- Improvements seen in both treatment groups, suggesting some natural variability or SOC effect
- Mechanistic explanation (neuroregeneration) inferred from external literature, not directly demonstrated in this analysis
Citation
Muscle & Nerve, 2026; 73:1109–1117