Botulinum Toxin Injections for Oral Neuropathic Pain (TRIGTOX)

• ClinicalTrials.gov Identifier: NCT03555916
• Recruitment Status: Recruiting
• First Posted: June 14, 2018
• Last Update Posted: April 24, 2019
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Karolinska Institutet; University of Aarhus
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Study Description

Brief Summary:

Peripheral painful traumatic trigeminal neuropathy (PPTTN) are poorly relieved by existing treatments which in addition induce many adverse effects. BTX, which blocks the exocytosis of neurotransmitters, can be captured by axonal retrograde transport in primary nociceptive neurons. Injected in the painful area, it might therefore inhibit the release of algogenic neurotransmitters, at both the peripheral and central levels and thus reduce pain. One study reported such an effect in neuropathic spinal pain. A recent study reported an analgesic effect in trigeminal neuralgia.

Condition or disease	Intervention/treatment	Phase
Trigeminal Neuropathy, Traumatic	Drug: BOTOX®, Allergan; Drug: Placebo	Phase 3

  Show Detailed Description

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Masking Description: Double Blind
• Primary Purpose: Treatment
• Official Title: Use of Botulinum Toxin (BTX) for the Treatment of Peripheral Painful Traumatic Trigeminal Neuropathy (PPTTN)
• Actual Study Start Date: April 4, 2019
• Estimated Primary Completion Date: November 2022
• Estimated Study Completion Date: April 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Drug; BOTOX®, Allergan treatment in 2 mL of saline solution (0.9% NaCl) treatment	Drug: BOTOX®, Allergan; 50 U BTX-A (BOTOX®, Allergan) powder diluted in 2 mL saline solution (0.9% NaCl) administrated at visit 2 by intra oral injection; Other Name: BOTOX
Placebo Comparator: Placebo; 2 mL of saline solution (0.9% NaCl) treatment	Drug: Placebo; 2 mL saline solution (0.9% NaCl) administrated at visit 2 by intra oral injection

Outcome Measures

Primary Outcome Measures :

1. Change from baseline of self-reported average pain intensity using 11-point numerical scale (0 = no pain; 10 = maximal pain imaginable) at one month [ Time Frame: before and one month after injection ]
   Self-reported average pain intensity from each morning's record in a diary concerning the last 24 hours during one week, before and one month after injection

Secondary Outcome Measures :

1. Pain measurement with the 11-point numerical scale of the Brief Pain Inventory (BPI) [ Time Frame: At baseline, 1, 3 and 6 months ]
   Pain recorded each morning in a diary (diary 2) concerning the last 24 hours, using the 11-point numerical scale (NS; 0 = no pain; 10 = maximal pain imaginable) of the Brief Pain Inventory (BPI) at 1 month, 3 months and 6 months. The least, average, and maximum pain intensity during the 7 days will be collected and compared to baseline.
2. Pain measurement with the neuropathic pain symptom inventory (NPSI) [ Time Frame: At baseline, 1, 3 and 6 months ]
   Items of the neuropathic pain symptom inventory (NPSI) will be recorded during the last 24 hours on 11-points (0-10 points) numerical scales.
3. Pain measurement with Visual Analogic Scale (VAS) [ Time Frame: At baseline, 1, 3 and 6 months ]
   Visual Analogic Scale (VAS) (from 0 mm [no pain relief] to 100 mm [maximal pain relief]).
4. Pain measurements with Clinical Global Impression - Improvement scale (CGI-I) [ Time Frame: At baseline, 1, 3 and 6 months ]
   The Clinical Global Impression - Improvement scale (CGI-I) (a 7-point scale rating from very much improved to very much worse) will be used .
5. Areas of pain [ Time Frame: At baseline, 1, 3 and 6 months ]
   The areas of main pain and referred pain will be reported directly from the patient to a soft foil, then digitized for measurement on Image J software.
6. Assessment of sensory deficit according to intraoral Quantitative Sensory Testing (QST) [ Time Frame: At baseline, 1, 3 and 6 months ]

   According to the conclusions of the European task force committee for intraoral quantitative sensory testing (QST), the QST is defined by :

   • Brush-induced allodynia will be evaluated stroking the skin with a standardized brush and will be considered as present if evoking a clear sensation of pain. The intensity of allodynia will be recorded on a 100 mm visual analog scale. Area of Brush-induced allodynia will be traced on a transparent plastic foil, and then digitized for measurement on Image J software.
   • Mechanical sensations (detection thresholds to non-painful stimuli) and pain thresholds will be measured with calibrated von Frey hairs (0.06-300gm) (Bioseb, France) (or electronic von Frey, Bioseb France).
   • Thermal sensations and pain thresholds (in °C) will be assessed with a thermoalgometer (TSA II; Medoc, Israel) with an intraoral thermode by the method of limits, with baseline temperatures adjusted to the patient's skin temperature .
7. Emotional state with Hospital Anxiety and Depression Scale (HADS) [ Time Frame: At baseline, 1, 3 and 6 months ]
   Emotional state using the Hospital Anxiety and Depression Scale (HADS) including 14 items scored as anxiety and depression scores (each on 21)
8. Emotional state with Brief Pain Inventory (BPI). [ Time Frame: At baseline, 1, 3 and 6 months ]
   Emotional state using items of the Brief Pain Inventory (BPI).
9. Movement and function [ Time Frame: At baseline, 1, 3 and 6 months ]
   Interference with oral function will be measured with the Brief Pain Inventory (BPI) (with the exclusion of the item "ability to walk" changed for "ability to chew" judged more relevant here) rated from 0 (does not interfere) to 10 (complete interference).
10. Quality of life with Geriatric Oral Health Assessment Index (GOHAI) [ Time Frame: At baseline, 1, 3 and 6 months ]
    Quality of life will be assessed with specific questionnaires Geriatric Oral Health Assessment Index (GOHAI)
11. Quality of life with Oral Health Impact Profile (OHIP) [ Time Frame: At baseline, 1, 3 and 6 months ]
    Quality of life will be assessed with specific Oral Health Impact Profile (OHIP)
12. Quality of life with items of Brief Pain Inventory (BPI). [ Time Frame: At baseline, 1, 3 and 6 months ]
13. Incidence of BTX-A - Emergent Adverse event [ Time Frame: At baseline, 1, 3 and 6 months ]
    Safety of BTX-A, particularly for potential systemic adverse effects, will be assessed throughout the study. Adverse events will be declared in the case report form (CRF).
14. Pain related to injections of BTX-A [ Time Frame: At baseline, 1, 3 and 6 months ]
    Pain related to injections will be rated as mild, moderate, or severe.
15. Time course of the pain: [ Time Frame: At baseline, 1, 3 and 6 months ]
    measurement of the time course of the pain throughout the day with a diary (diary 1) in which the patient reports his/her pain every hour on a numeric scale (0-10) during 7 days.
16. Thermography [ Time Frame: At baseline, 1, 3 and 6 months ]
    measurement (in °C), by a camera with a thermal sensitivity

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion criteria

1. Informed consent form signed
2. Adult patients, age 18 -75 y.o.
3. Medical coverage (excepted AME)
4. Understanding of all medical information
5. Subjects fulfilling diagnostic criteria for Peripheral painful traumatic trigeminal neuropathy (PPTTN)
6. Pain in one or several branches of the trigeminal nerve
7. History of surgical treatment (including endodontic treatments) in the painful area
8. Pain in the area experienced in the 3 months following the treatment
9. pain almost every day for at least 6 months
10. VAS ≥ 30 /100 mm
11. Primary painful area limited to one dental quadrant
12. Presence of at least one positive (hyperalgesia, allodynia, numbness or swelling) and/or negative (anesthesia or hypoesthesia) sign of neurological dysfunction
13. Pain cannot be attributed to another cause

Exclusion criteria

1. Patients with impaired communication
2. Pregnancy, breastfeeding or planning pregnancy within the period of the study
3. Women of childbearing potential (WOCBP), adequate method of contraception within the period of the study
4. Orofacial pain other than PPTTN unless clearly identifiable TMD (arthralgia, muscle pain or disc displacement)
5. Contra-indications for BTX-A (for example diseases of the neuromuscular junction, known hypersensitivity to BTX-A etc.)
6. Known coagulation disorders
7. Major depression (score > XX HADS scale)
8. Background of drug consumption or excessive alcohol consumption (3 units of alcohol a day)
9. current legal dispute with a dental practitioner
10. Former use of BTX for esthetic purpose
11. Dysphagia
12. Aspiration pneumonitis
13. Troubles with bladder control
14. Concomitant use of analgesics with dosage modification since less one month before inclusion in the study
15. Topical applications of drugs and anesthetics which cannot be interrupted one week before visit sessions
16. Treatment with aminoglycosides in the three months preceding the selection
17. Participation to another interventional clinical study

Contacts and Locations

Contacts

Contact: Yves BOUCHER, DDS,PhD; 01 42 16 14 56; yves.boucher@univ-paris-diderot.fr

Locations

France

Groupe Hospitalier Pitié-Salpêtrière; Recruiting

Paris, France

Contact: Boucher Yves, DDS, PhD 01 42 16 14 56 yves.boucher@univ-paris-diderot.fr

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Karolinska Institutet

University of Aarhus

Investigators

• Principal Investigator: Yves BOUCHER, DDS,PhD; Assistance Publique - Hôpitaux de Paris

More Information

Publications:

Moreau N, Dieb W, Descroix V, Svensson P, Ernberg M, Boucher Y. Topical Review: Potential Use of Botulinum Toxin in the Management of Painful Posttraumatic Trigeminal Neuropathy. J Oral Facial Pain Headache. 2017 Winter;31(1):7-18. doi: 10.11607/ofph.1753. Review.

• Responsible Party: Assistance Publique - Hôpitaux de Paris
• ClinicalTrials.gov Identifier: NCT03555916 History of Changes
• Other Study ID Numbers: P150901; 2017-002353-11 ( EudraCT Number )
• First Posted: June 14, 2018
• Last Update Posted: April 24, 2019
• Last Verified: April 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Assistance Publique - Hôpitaux de Paris:

BOTOX®-Allergan; PPTTN; Pain measurements

Additional relevant MeSH terms:

Trigeminal Nerve Diseases; Trigeminal Nerve Injuries; Facial Neuralgia; Facial Nerve Diseases; Mouth Diseases; Stomatognathic Diseases; Cranial Nerve Diseases; Nervous System Diseases; Cranial Nerve Injuries; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Pharmaceutical Solutions; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA; Acetylcholine Release Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Neuromuscular Agents; Peripheral Nervous System Agents