Botox as a treatment for chronic nerve pain

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Aarhus Universitetshospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

completed 18 Nov 2024

Decision date (initial)

2023-10-16

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

Salling Fonden

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

The main objective is to investigate the pain-relieving effect of perineural botox injection in patients with chronic cutaneous neuropathic pain

Secondary objectives 1

1. Secondary objectives include time to onset of the pain relieving effect, pain scores in rest, activity and at provocation, patient satisfaction, effect of the treatment on sleep and activity level and side effects.

Conditions and MedDRA coding

Neuropathy

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Age ≥ 18 years
2. American Society of Anesthesiologists physical status classification score (ASA) I-III
3. Suitable candidate for injection of botox (sponsor-investigator's assessment)
4. Informed consent
5. Able to subjective evaluation of pain
6. Able to read and understand Danish and to read, understand and sign the informed consent form
7. Worst pain in rest/activity/at provocation NRS (Numeric rating scale) score ≥ 5 in the primary area(s) of pain for at least 6 months at the time of inclusion
8. Has tried relevant medical first line treatment for the neuropathic pain where the treatment is currently stable or terminated
9. The localization of the painful skin area is neuro-anatomically plausible in relation to the suspected nerve damage (sponsor-investigator's assessment)
10. In one or more painful and neuro-anatomically relevant area is at least one of the following criteria present when compared to the contralateral side: (1) Hypoesthesia/anesthesia for touch (brush); Hypoesthesia/anesthesia for moderate cold (alcohol swab); (3) Hypoesthesia/anesthesia for moderate heat (thermo roller); (4) Hypoesthesia/anesthesia for pinprick (Neuropen); (5) Allodynia for touch (brush); (6) Allodynia for moderate cold (alcohol swab); (7) Allpdynia for moderate heat (Thermo roller); (8) Hyperalgesia for pinprick (Neuropen)
11. Diagnostic ultrasound guided nerve block performed at the Nerve Injury Clinic at Aarhus University Hospital within the last 28 days before inclusion, where injection of local anesthetic around the neuropathic nerve(s) resulted in a pain reduction to NRS score 3 or below at the same provocation which previously resulted in maximal pain

Exclusion criteria 13

1. Know allergy towards Botulinum A or any substances listed in "Produktresumé for ”BOTOX, pulver til injektionsvæske, opløsning 50, 100 og 200 Allergan-enheder”
2. Not able to cooperate
3. Infection in the area around the site of injection
4. Significant competing pain which could interfere with the estimation of the treatment effect (sponsor-investigator's assessment)
5. Current diagnosis of progressive neurological disease
6. Uncontrolled, severe systemic disease
7. Previous interventional pain treatment (e.g., spinal cord stimulation, cryoneurolysis, botox) without relevant effect for the same persisting, cutaneous neuropathic pain (note that Transcutaneous Electrical Nerve Stimulation, TENS, is not considered interventional)
8. Previous injection of botox for the same persisting, cutaneous neuropathic pain
9. Number of nerves where the diagnostic nerve block provides pain relief is greater than 3
10. Breast feeding or pregnancy. All women without verified menopause will be tested for pregnancy (urine HCG) on the day of inclusion. Verified menopause is defined as > 1 year since the last period without any other explanation and age >45 years
11. Abuse of alcohol or drugs (illegal and prescription drugs) assessed by sponsor-investigator
12. Participation in other clinical studies which may interfere with the present (sponsor-investigator's assessment)
13. Any ongoing patient case/complaint related to the present cutaneous neuropathic pain

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The number of responders in the botox group versus the placebo group. Responders are defined as patients who at the 4 weeks follow-up, describe the pain-relieving effect in the neuropathic area(s) during the last 48 hours as mild, moderate or good.

Secondary endpoints 14

1. Change in overall pain score (NRS) estimated during the last 48 hours at the time of the 4-week follow-up in botox versus placebo group
2. Change in pain score (NRS) at rest/activity/provocation in the neuropathic area(s) estimated during the last 48 hours at the time of the 4-week follow-up in botox versus placebo group
3. Time to onset of the pain-relieving effect of botox, where effect is defined as mild, moderate or good pain-relieving effect for at least 48 hours
4. Time to onset of maximal pain-relieving effect of botox
5. Change in overall maximal pain score (NRS) for botox responders
6. Number of patients in the botox group with maximal pain-relieving effect later than at the 4-week follow-up
7. Overall satisfaction (not satisfied/satisfied) with the treatment in the botox versus placebo group evaluated at the 4- week follow-up
8. Change in sleep quality (worse, unchanged, improved) in the botox versus placebo group evaluated at the 4-week follow-up
9. Change in activity level (lower, unchanged, higher) in the botox versus placebo group evaluated at the 4-week follow-up
10. "Patient global impression of change" in botox versus placebo groups evaluated at the time of 4-week-follow-up
11. Duration of pain relieving effect (number of days) after injection of botox estimated in botox responders.
12. Number of patients in the botox group who would recommend the treatment to other patients
13. Number of patients in the botox group who would want to receive botox treatment again in the future
14. Adverse events estimated from the time og injection of trial medication until the end of the trial

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Aarhus Universitetshospital

Sponsor organisation

Aarhus Universitetshospital

Address

Palle Juul-Jensens Boulevard 99

City

Aarhus N

Postcode

8200

Country

Denmark

Scientific contact point

Organisation

Aarhus Universitetshospital

Contact name

Thomas Fichtner Bendtsen

Public contact point

Organisation

Aarhus Universitetshospital

Contact name

Thomas Fichtner Bendtsen

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 3 files

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

Application history

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