Diabetes, Diabetes Complications, Diabetic Neuropathy
Conditions
Keywords
Diabetic neuropathy, Pain, Acarbose
Brief summary
This Phase II pragmatic hybrid effectiveness-implementation trial tests whether acarbose, titrated using continuous glucose monitoring (CGM) to blunt post-prandial excursions, reduces 4-week pain area-under-the-curve (AUC) versus placebo in adults with painful diabetic peripheral neuropathy (DPN) and high glycemic variability. Secondary objectives assess CGM variability metrics, microvascular reactivity, inflammatory markers, safety, and feasibility of a pharmacist-led titration workflow using loaner CGMs across multi-region community clinics.
Detailed description
Adults with T2D, painful DPN, and high CGM variability (e.g., MAGE \>50 mg/dL on run-in) are randomized 1:1 to acarbose vs matching placebo for 4 weeks, on stable background analgesics. A standardized pharmacist-led algorithm escalates acarbose to target post-prandial spikes, guided by blinded CGM trend review. The primary endpoint is 4-week daily pain AUC captured via ePRO. Key secondary endpoints include changes in MAGE and time-in-range (TIR), skin microvascular reactivity (laser speckle), serum IL-6, patient global impression of change, rescue-analgesic use, and adverse events. Implementation outcomes (acceptability, feasibility, adoption, cost) are collected to inform scale-up in HIC and LMIC community settings.
Interventions
DRUGAcarbose 50 mg
Acarbose with meals; pharmacist-led titration (e.g., 50 mg TID → up to 100 mg TID as tolerated)
DRUGPlacebo
Matching placebo; identical titration schedule
Sponsors
Shifa International Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Inclusion: * Age 18-75 years. * Type 2 diabetes ≥1 year; HbA1c 7.0-10.0% within 8 weeks of randomization. * Painful DPN meeting clinical criteria; average daily pain NRS ≥4 during run-in. * High CGM variability on 7-10 day run-in (e.g., MAGE \>50 mg/dL). * Stable analgesic regimen ≥4 weeks pre-baseline. * Able to use CGM and ePRO; provides informed consent. Exclusion: * Type 1 diabetes; non-diabetic neuropathies. * Contraindications to acarbose (e.g., chronic intestinal malabsorption, inflammatory bowel disease). * eGFR \<45 mL/min/1.73 m²; significant hepatic disease (ALT/AST \>3× ULN). * Use of α-glucosidase inhibitors within 3 months. * Recent change (\<3 months) in GLP-1/GIP agonists, SGLT2i, or basal/bolus insulin strategy. * Pregnancy/lactation; other conditions compromising safety/assessments.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Daily pain AUC | baseline→Week 4 | Daily pain AUC (ePRO; 0-10 NRS). Method: trapezoidal AUC of daily NRS scores; higher AUC = worse pain. Daily pain area under the curve derived from the Numeric Rating Scale for Pain (NRS). The NRS ranges from 0 to 10, where 0 = no pain and 10 = worst imaginable pain. Higher scores indicate worse pain. AUC is calculated using the trapezoidal method from daily NRS scores over the assessment period. Higher AUC values indicate greater overall pain burden. |
| CGM MAGE (mg/dL) | baseline→Week 4 | CGM MAGE (mg/dL) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CGM Time-in-Range (70-180 mg/dL, %) | baseline→Week 4 | CGM Time-in-Range (70-180 mg/dL, %) |
| Skin microvascular reactivity | baseline→Week 4 | Skin microvascular reactivity by laser speckle contrast imaging |
| Serum IL-6 | baseline→Week 4 | Serum IL-6 (pg/mL) |
| Patient Global Impression of Change (PGIC) | Week 4 | Patient Global Impression of Change (PGIC). Patient Global Impression of Change (PGIC) assessed on a 7 point Likert scale ranging from 1 = very much improved to 7 = very much worse. Lower scores indicate improvement; higher scores indicate worsening. |
Countries
Pakistan
Outcome results
None listed