Peripheral TMD Pain Mechanisms and the Effect by Botulinum Toxin A
ConditionTemporomandibular Disorders
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age20-45
SponsorKarolinska Institutet
About this trial
The goal of this clinical trial is to investigate the effect of botulinum toxin on neurons' plasticity in the masseter muscle in humans with and without painful myogenous temporomandibular disorders (TMDM). The main questions it aims to answer are:
* does treatment with botulinum toxin alter gene expressions, epigenetic signatures, and cells plasticity in the masseter muscles of TMDM patients? * do any such changes differ between patients with local and regional TMDM? * does treatment with botulinum toxin influence pain characteristics (intensity, frequency, and sensibility) and other variables in patients with TMDM and are there correlations between significantly changed expression of biomarkers and other variables?
Participants will be examined with a questionnaire, clinical examination (including quantitative sensory testing; QST), and microbiopsy sampling from one of the masseter (MM) and anterior tibialis (AT) muscles and are then randomized to treatment with botulinum toxin or control (isotonic saline). Follow-ups occur after one and three months for all patients, and six months with questionnaire, clinical examination, and collection of post-treatment microbiopsies to see if botulinum toxin alter peripheral molecular events and clinical variables.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
a diagnosis of TMDM myalgia or myofascial pain according to the DC/TMD criteria
females with adequate contraceptives and a negative pregnancy test
pain upon digital palpation of at least one of the masseter muscle
a characteristic pain intensity of > 40/100
Disqualifiers
difficulties understanding the Swedish language
systemic inflammatory connective tissue diseases
widespread pain
neuromuscular disorders
Trial design
Design model
Parallel
Treatments tested in this trial
Botulinum toxin type A
DrugRandomized double-blind administration
Isotonic saline 0,9%
DrugRandomized double-blind administration
Treatment groups
100 Participants
are divided into 2 treatment groupsGroup A: Botulinum toxinActive comparator 1 intervention
Group B: Isotonic salinePlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
Change of gene expression measured with bulk RNA-seq
Gene expression in the anterior tibialis muscle (internal control) will be subtracted from the masseter and the patients will then be clustered according to DEGs and compared to baseline.
Time frame
1-6 months2
Change of RNA expression measured with single-cell RNA (scRNA) seq/spatial trnascriptomics.
ScRNA-seq will be analyzed by SEURAT
Time frame
1-6 months3
Change of expression of sensory neuron markers measured with IHC
The expression will be measured as the change of frequency (%) of selected sensory neuron markers.
Time frame
1-6 months4
Change of proteome measured with proteomics
The expression wil be measured with two-dimensional gel electrophoresis, followed by liquid chromatography-tandem mass spectrometry and protein network analyses.
Time frame
1-6 monthsSecondary outcomes
1
Change of pain intensity compared to baseline using 0-10 numeric rating scales (NRS)
Assessed with the Brief Pain Inventory and includes assessment of the current and the worst, average, and least pain intensity during the last week, each scored on 0-10 numeric rating scale. The worst, average, and current pain can be used to calculate the Characteristic Pain Intensity (0-100) which is the mean score of the three assessments multiplied with ten.
Time frame
1-3 months2
Global improvement using Patient Global Impression of Change Scale (PGIC)
Assessed with the 7-point PGIC with the alternatives: 0 = eliminated, 1 = much improved, 2 = improved, 3 = unchanged, 4 = impaired, 5 =much impaired and 6 = very much impaired.
Time frame
1-3 months3
Change of pain quality compared to baseline using the McGill Pain questionnaire (MPQ)
Assessed with the MPQ Short-Form which includes 15 adjectives that can be used to describe pain, each scored according to severity (0-3). The total score is calculated.
Time frame
1-3 months4
Number of participants with adverse events assessed with questionnaire
The participant lists any adverse event occurring during the week after injection and rate them as mild, moderate or severe.
Time frame
1 weekOther outcomes
1
Change of thermal detection and pain thresholds measured with Thermotest.
The program is set at first recording warmth (WST) and cold detection thresholds (CDT) four times and then cold (CPT) and heat pain thresholds (HPT) three times. The mean of the recording for each threshold is calculated by the program software and used in analyses.
Time frame
1-3 months2
Change of pin-prick pain measured with Medipin
The perceived magnitude of a single pin-prick stimulus is assessed using a Medipin® (Medipin Limited, Hertfordshire, United Kingdom). The device is applied perpendicular to the skin for 1-2 seconds. Then the participant is asked to give a pain rating representing the pain at the end of the stimuli using a 0-100 NRS.
Time frame
1-3 months3
Change of temporal summation pain compared to baseline
Temporal summation will be evoked with a 1.0 kg palpometer. The stimulus will be applied 10 times at the masseter muscle for 2 s with 1 s interval and pain intensity will be recorded after the 1st, 5th, and 10th stimulation on a 0-10 NRS.
Time frame
1-3 months4
Change of pressure pain threshold (PPT) compared to baseline
The PPT (kPa) will be recorded over the masseter muscle with an electronic algometer as the average of three recordings
Time frame
1-3 monthsSponsors and contacts
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Source ClinicalTrials.gov