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Perineural Injections of Incobotulinumtoxin-A for Diabetic Neuropathic Pain of the Lower Extremities (PINBOT)

Primary Purpose

Diabetic Neuropathy, Painful

Status
Recruiting
Phase
Phase 2
Locations
Denmark
Study Type
Interventional
Intervention
Incobotulinumtoxin-A 100 UNIT Injection
Saline
Sponsored by
Rigshospitalet, Denmark
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetic Neuropathy, Painful

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Are 18 years or older Are diagnosed with diabetes type I or II Score 3 or above on the Doleur Neuropathique 4 interview section Suffer from pain of the lower extremities which is considered by the participant as their dominant overall dominant pain is rated at least 4 out of 10 of the NRS pain scale in both legs (on average over the past 7 days) is present in both feet, roughly symmetrically. has been present for at least 6 months Show sensory deficits and/or allodynia or hyperalgesia in the painful area, consistent with the IASP definition of probable chronic neuropathic pain40. Are in a stable analgesic treatment regime for at least 1 month prior to inclusion and for the duration of the study Are using an approved, safe contraceptive (for premenopausal women) Speak, read, and understand Danish Exclusion Criteria: • Have a known allergy or hypersensitivity to BonT-A Have been treated with BonT in the last 6 months. Are diagnosed with myasthenia, Eaton-Lambert syndrome, or amyotrophic lateral sclerosis Have a known malignant condition Have an ongoing infection in the area of injection Are expecting to change their pain medication during the study period Have been treated with topical agents such as capsaicin or lidocaine products in the affected areas for at least 3 months prior to inclusion Are diagnosed with a competing cause of central or peripheral neuropathic pain, or other painful chronic conditions of the lower extremities, such as: spinal stenosis claudication previous trauma or nerve injury cancer related pain Have a psychiatric condition that affects their completion of the study, as assessed by the investigator. Are active abusers of alcohol or illegal substances Are using or receiving treatment with cannabis products of any kind Are pregnant or planning pregnancy during the study period Score more than 12 on the Charlson Comorbidity Index

Sites / Locations

  • Rigshospitalet GlostrupRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Incobotulinumtoxin-A

Placebo

Arm Description

100 units of incobotulinumtoxin-A in 5ml of sterile saline around both distal ischial nerves.

5ml sterile saline with small amounts of human albumin and sucrose (identical to binding agents in active vials)

Outcomes

Primary Outcome Measures

Changes in daily neuropathic pain scores
Differences in pain scores, as measured by the Numeric Rating Scale (0-11), between groups.

Secondary Outcome Measures

Use of rescue medication
Recorded using pain diary with simple Yes/No for use of any rescue medication. Changes in use of rescue medication over time and between groups.
Neuropathic Pain Symptom Inventory
Changes in NPSI total and sub-scores over time and between groups.
Health-related quality of life
EQ-5D-5L
Activities of daily living
Canadian Occupational Outcome Measure (COPM)
Physical activity
Grimby-Saltin Physical Activity Scale, Danish Version (PAS-2-DK)
Depression symptoms
Beck Depression Inventory II (BDI-II)
Adverse events
Incidence, severity and character of adverse, compared between active and placebo groups
Motorfunction of the lower legs.
Oxford MRC Muscle Power Assessment
Sensory function
Sensation of the lower legs and feet, as measured by Quantitative Sensory Testing, according to the DFNS protocol.

Full Information

First Posted
October 31, 2022
Last Updated
May 17, 2023
Sponsor
Rigshospitalet, Denmark
Collaborators
Merz Pharmaceuticals GmbH, Toyota Foundation Denmark, Steno Diabetes Center Zealand Region, Shipwright Per Henriksen, R., and wife Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT05623111
Brief Title
Perineural Injections of Incobotulinumtoxin-A for Diabetic Neuropathic Pain of the Lower Extremities
Acronym
PINBOT
Official Title
Perineural Injections of Incobotulinumtoxin-A for Diabetic Neuropathic Pain of the Lower Extremities: A Double-blind, Randomized, Placebo-controlled Study
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 1, 2023 (Anticipated)
Primary Completion Date
October 1, 2025 (Anticipated)
Study Completion Date
February 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Rigshospitalet, Denmark
Collaborators
Merz Pharmaceuticals GmbH, Toyota Foundation Denmark, Steno Diabetes Center Zealand Region, Shipwright Per Henriksen, R., and wife Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The goal of this clinical trial is to test perineural injections (injections around a nerve) of incobotulinumtoxin-A in participants with diabetic nerve pain of the feet and lower legs. The main questions it aims to answer are: Is the treatment safe and effective? Does the treatment affect participants quality of life, depression, physical activity, daily life, and sensation? Participants will be treated every 12 weeks, for a total of 24 weeks, with either incobotulinumtoxin-A or a placebo.
Detailed Description
This study is a randomized, double-blind, placebo-controlled trial, investigating the safety, efficacy, use of rescue medication, and impact on NPSI scores, health-related QoL, activities of daily living (ADLs) and levels of physical activity of perineural incobotulinumtoxin-A (iBonT-A) or placebo injections, in persons with DNP of the lower extremities. Participants will be randomly assigned via simple block randomization to receive either 100 units of iBonT-A in each leg (total of 200 units), or a placebo in each leg, injected perineurally around both distal sciatic nerves once every 12 weeks, for a total of 24 weeks. Injections are performed with sonographic guidance by an experienced operator. Contents of the blinded vials, containing either 100 U of iBonT-A or a placebo consisting of small amounts of sucrose and albumin are diluted in 5 ml of sterile saline. The injection point is just distal to the sciatic nerve bifurcation. The skin is penetrated from the lateral side using a non-cutting needle (Pajunk, SonoBlock, 22G x 80 mm, Facet S Tip). With the needle in plane in relation to the ultrasound probe, the nerves are visualized in short axis. The needle tip is placed inside the common sheath surrounding the tibial and peroneus communis nerves. The location of the needle tip is verified with small boli of sterile saline solution in combination with ultrasound. Correct distribution of the injectant is confirmed with dynamic scanning. Fluid distention must be seen around both components. When confirmation of optimal needle placement the 100 units iBonT-A or placebo is injected. The procedure is repeated for both legs. Participants will be asked to rate their neuropathic pain once a day, as well as register their daily use of rescue medication. Secondary outcome measures will be rated at baseline and at 4, 12, 16 and 24 weeks. Safety information consists of adverse events recording, as well as motorfunction and sensory changes over time.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetic Neuropathy, Painful

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
2-armed active/placebo 1:1 ratio
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Incobotulinumtoxin-A
Arm Type
Active Comparator
Arm Description
100 units of incobotulinumtoxin-A in 5ml of sterile saline around both distal ischial nerves.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
5ml sterile saline with small amounts of human albumin and sucrose (identical to binding agents in active vials)
Intervention Type
Drug
Intervention Name(s)
Incobotulinumtoxin-A 100 UNIT Injection
Intervention Description
Perineural injection
Intervention Type
Drug
Intervention Name(s)
Saline
Intervention Description
Placebo containing trace amounts of human albumin and sucrose, diluted with 5ml of sterile saline.
Primary Outcome Measure Information:
Title
Changes in daily neuropathic pain scores
Description
Differences in pain scores, as measured by the Numeric Rating Scale (0-11), between groups.
Time Frame
Recorded once daily for 1 week prior to first injection and daily for the duration of the study. Outcome is defined as differences in change from baseline of average daily and weekly pain scores between groups.
Secondary Outcome Measure Information:
Title
Use of rescue medication
Description
Recorded using pain diary with simple Yes/No for use of any rescue medication. Changes in use of rescue medication over time and between groups.
Time Frame
Recorded once daily for 1 week prior to first injection and daily for the duration of the study. Defined as differences in change from baseline of average days per week of rescue medication usage across the study period.
Title
Neuropathic Pain Symptom Inventory
Description
Changes in NPSI total and sub-scores over time and between groups.
Time Frame
Baseline, 4 weeks, 12 weeks, 16 weeks, 24 weeks.
Title
Health-related quality of life
Description
EQ-5D-5L
Time Frame
Baseline, 4 weeks, 12 weeks, 16 weeks, 24 weeks.
Title
Activities of daily living
Description
Canadian Occupational Outcome Measure (COPM)
Time Frame
Baseline, 4 weeks, 12 weeks, 16 weeks, 24 weeks.
Title
Physical activity
Description
Grimby-Saltin Physical Activity Scale, Danish Version (PAS-2-DK)
Time Frame
Baseline, 4 weeks, 12 weeks, 16 weeks, 24 weeks.
Title
Depression symptoms
Description
Beck Depression Inventory II (BDI-II)
Time Frame
Baseline, 4 weeks, 12 weeks, 16 weeks, 24 weeks.
Title
Adverse events
Description
Incidence, severity and character of adverse, compared between active and placebo groups
Time Frame
Number and nature of adverse events compared between groups at 24 weeks.
Title
Motorfunction of the lower legs.
Description
Oxford MRC Muscle Power Assessment
Time Frame
Baseline, 4 weeks, 12 weeks, 16 weeks, 24 weeks.
Title
Sensory function
Description
Sensation of the lower legs and feet, as measured by Quantitative Sensory Testing, according to the DFNS protocol.
Time Frame
Baseline, 4 weeks, 12 weeks, 16 weeks, 24 weeks.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Are 18 years or older Are diagnosed with diabetes type I or II Score 3 or above on the Doleur Neuropathique 4 interview section Suffer from pain of the lower extremities which is considered by the participant as their dominant overall dominant pain is rated at least 4 out of 10 of the NRS pain scale in both legs (on average over the past 7 days) is present in both feet, roughly symmetrically. has been present for at least 6 months Show sensory deficits and/or allodynia or hyperalgesia in the painful area, consistent with the IASP definition of probable chronic neuropathic pain40. Are in a stable analgesic treatment regime for at least 1 month prior to inclusion and for the duration of the study Are using an approved, safe contraceptive (for premenopausal women) Speak, read, and understand Danish Exclusion Criteria: • Have a known allergy or hypersensitivity to BonT-A Have been treated with BonT in the last 6 months. Are diagnosed with myasthenia, Eaton-Lambert syndrome, or amyotrophic lateral sclerosis Have a known malignant condition Have an ongoing infection in the area of injection Are expecting to change their pain medication during the study period Have been treated with topical agents such as capsaicin or lidocaine products in the affected areas for at least 3 months prior to inclusion Are diagnosed with a competing cause of central or peripheral neuropathic pain, or other painful chronic conditions of the lower extremities, such as: spinal stenosis claudication previous trauma or nerve injury cancer related pain Have a psychiatric condition that affects their completion of the study, as assessed by the investigator. Are active abusers of alcohol or illegal substances Are using or receiving treatment with cannabis products of any kind Are pregnant or planning pregnancy during the study period Score more than 12 on the Charlson Comorbidity Index
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Marc Klee Olsen, MD
Phone
+4538633030
Email
marc.klee.olsen@regionh.dk
First Name & Middle Initial & Last Name or Official Title & Degree
Trine Thomsen, MsC
Phone
+4538632712
Email
trine.hoermann.thomsen@regionh.dk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bo Biering-Sørensen, MD
Organizational Affiliation
Neurological Pain Clinic, Rigshospitalet
Official's Role
Study Director
Facility Information:
Facility Name
Rigshospitalet Glostrup
City
Glostrup
ZIP/Postal Code
2600
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marc K Olsen, MD
Email
marc.klee.olsen@regionh.dk

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Study data will be published in anonymised format as supplementary material to publications. Study protocol, SAP, ICH And analytic code available upon request.
IPD Sharing Time Frame
Data will be published as supplementary material to publications.
IPD Sharing Access Criteria
Open Access

Learn more about this trial

Perineural Injections of Incobotulinumtoxin-A for Diabetic Neuropathic Pain of the Lower Extremities

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