Perineural injections of incobotulinumtoxin-A for diabetic neuropathic pain of the lower extremities: A double-blind, randomized, placebo-controlled study (PINBOT)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Rigshospitalet

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18], Diseases [C] - Nervous System Diseases [C10]

Trial duration

7 Aug 2023 → ongoing

Decision date (initial)

2022-11-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merz Pharmaceutical

External identifiers

EU CT number

2022-500727-68-01

WHO UTN

U1111-1280-3419

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

This study will investigate the efficacy and safety of bilateral perineural incobotulinumtoxinA (iBonT-A) injections in persons with diabetic neuropathic pain of the lower extremities.

Secondary objectives 8

1. To establish baseline characteristics and changes in sensory profiles (measured by Quantitative Sensory Testing) of the lower extremities, in participants with diabetic neuropathic pain of the lower extremities, before, during, and after perineural injections of incobotulinumtoxin-A around the distal ischial nerves.
2. To investigate effects on muscle power of the lower extremities (as measured by the Oxford MRC scale) in participants with diabetic neuropathic pain of the lower extremities, before, during, and after perineural injections of incobotulinumtoxin-A around the distal ischial nerves.
3. To investigate the effects of perineural incobotulinumtoxinA (iBonT-A) injections around the distal ischial nerves in persons with diabetic neuropathic pain of the lower extremities on self-reported health related quality of life (as measured by the EQ-5D-5L)
4. To investigate the effects of perineural incobotulinumtoxinA (iBonT-A) injections around the distal ischial nerves in persons with diabetic neuropathic pain of the lower extremities on activities of daily living as measured by the Canadian Occupational Perfomance Measure.
5. To investigate the effects of perineural incobotulinumtoxinA (iBonT-A) injections around the distal ischial nerves in persons with diabetic neuropathic pain of the lower extremities on presence of and severity of depressive symptoms, as measured by the BDI-II questionniare
6. To investigate the effects of perineural incobotulinumtoxinA (iBonT-A) injections around the distal ischial nerves in persons with diabetic neuropathic pain of the lower extremities on levels of physical activity, as measured by the Grimby-Saltin Physical Activity Scale (Danish version)
7. To investigate the effects of perineural incobotulinumtoxinA (iBonT-A) injections around the distal ischial nerves in persons with diabetic neuropathic pain of the lower extremities on self-reported use of rescue medication.
8. To investigate the effects of perineural incobotulinumtoxinA (iBonT-A) injections around the distal ischial nerves in persons with diabetic neuropathic pain of the lower extremities on characteristics and severity of specific symptoms of neuropathic pain, as measured by the Neuropathic Pain Symptom Inventory questionnaire.

Conditions and MedDRA coding

Diabetic neuropathic pain

Study design 1 period

Regulatory references

Plan to share IPD

No

IPD plan description

.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 18 years of age or older
2. Diagnosed with diabetes mellitus, type I or II
3. Diagnosed with diabetic neuropathic pain that is a) by the participant as their dominant overall dominant pain b) rated at least 4 out of 10 of the NRS pain scale in both legs on average over the past 7 days c) fulfils the IASP criteria for Definite chronic neuropathic pain d) has been verified using nerveconduction studies e) present in both legs, below the knee f) has been present for at least 6 months
4. In a stable analgesic treatment regime for at least 1 month prior to inclusion and for the duration of the study
5. Not been treated with topical agents such as capsaicin or lidocaine products in the affected areas for at least 3 months prior to inclusion
6. Using an approved, safe contraceptive (for premenopausal women)
7. Speak, read, and understand Danish

Exclusion criteria 12

1. A known allergy or hypersensitivity to botulinumtoxin
2. Treated with botulinumtoxin in the last 6 months
3. Diagnosed with myasthenia, Eaton-Lambert syndrome, or amyotrophic lateral sclerosis
4. A known malignant condition
5. An ongoing infection in the area of injection (right above the knee joint)
6. Expect to change their pain medication during the study period
7. Diagnosed with a competing cause of central or peripheral neuropathic pain, or other painful chronic conditions of the lower extremities, such as spinal stenosis, claudicatio, previous traume or nerve injury or cancer related pain.
8. A psychiatric condition that affects their completion of the study, as assessed by the investigator.
9. Active abusers of alcohol or illegal substances
10. Using or receiving treatment with cannabis products of any kind
11. Pregnant or planning pregnancy during the study period
12. A score of more than 25 on the Charlson Comorbidity Index

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Efficacy of pain relief of bilateral perineural injections of incobotulinumtoxin-A around the distal ischial nerve. The primary outcome will be tested using a generalised linear mixed model of repeated measures of daily (or weekly means) of pain scores (NRS), comparing active and placebo groups for 24 weeks, with the mean baseline pain score of each group as a covariate.

Secondary endpoints 8

1. QST: Sensory profiles will be generated for each QST sample as stipulated by the DFNS protocol. Accordingly, recorded values will be z-transformed by subtracting the mean value of an age- and sex matched reference group. Z-scores of >1.96 or <−1.96 i.e., falling outside the 95% confidence interval for matched healthy controls, will be considered abnormal. Absolute scores will also be compared before and after treatment, and between the two groups.
2. Muscle power: Muscle power of the lower extremities over time for active and placebo groups will be compared to baseline and between groups using a generalised linear mixed-model of repeated measures, with pre-treatment baseline values as a covariate.
3. HR-QoL:EQ-5D-5L visual analogue scale of self-perceived health scores for active and placebo groups will be compared to baseline and between groups using a generalised linear mixed-model of repeated measures, with pre-treatment baseline values as a covariate.
4. ADL: COPM scores for active and placebo groups will be compared to baseline and between groups using a generalised linear mixed-model of repeated measures, with pre-treatment baseline values as a covariate.
5. Depression: BDI-II total- and subscores for active and placebo groups will be compared to baseline and between groups using a generalised linear mixed-model of repeated measures, with pre-treatment baseline values as a covariate.
6. Physical activity: PAS-2-DK scores for active and placebo groups will be compared to baseline and between groups using a generalised linear mixed-model of repeated measures, with pre-treatment baseline values as a covariate.
7. Rescue medication: Average days with use of rescue medication per week for active and placebo groups will be compared to baseline and between groups using a generalised linear mixed-model of repeated measures, with pre-treatment baseline values as a covariate.
8. Neuropathic pain symptoms: NPSI total and subscores for active and placebo groups will be compared to baseline and between groups using a generalised linear mixed-model of repeated measures, with pre-treatment baseline values as a covariate.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Rigshospitalet

Sponsor organisation

Rigshospitalet

Address

Nordre Ringvej 57

City

Glostrup

Postcode

2600

Country

Denmark

Scientific contact point

Organisation

Rigshospitalet

Contact name

Neurological Pain Clinic, Rigshospitalet Glostrup

Public contact point

Organisation

Rigshospitalet

Contact name

Neurological Pain Clinic, Rigshospitalet Glostrup

Third parties 2

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications