Myofacial Pain SyndromeEarly Phase 1NCT05605886
Botulinum Toxin A in Patients With Myofascial Pain Syndrome With and Without Zinc Supplementation
A Early Phase 1 study testing Solvazinc 50mg in people with Myofacial Pain Syndrome and Botulinum Toxin, run by Cairo University at 1 site in Egypt.
Trial summary
Research question: Dose the use of oral zinc supplement improve the effects of botulinum toxins injection in patients with myofascial pain dysfunction syndrome? Statement of the problem: MPDS Patients treated with botulinum toxin A injection usually suffers from return of the symptoms which requires successive… Read more about this study
- Who is it for?
- Ages 17 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Myofacial Pain Syndrome, Botulinum Toxin
- What is being tested?
- Solvazinc 50mg
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteEgypt
- Study dates
- 20 May 2022to 20 May 2023
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 17 to 50 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Patients with myofascial pain
- Both genders males and females will be included.
- Ages from 17:50 Y
- General good health
- With complete dentation
Who cannot join
- Subjected to irradiation in the head and neck area less than 1 year ago
- Edentulous patients
- Patient with recent trauma.
- Poor motivation.
- Active infection area related to masseter or temporalis.
- Patient with anti-tetanus vaccine 1-3 m before experiment
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Botulinum Toxin A in Patients With Myofascial Pain Dysfunction Syndrome With and Without Zinc Supplementation (Randomized Controlled Trial)
Research question:
Dose the use of oral zinc supplement improve the effects of botulinum toxins injection in patients with myofascial pain dysfunction syndrome?
Read more
Statement of the problem:
MPDS Patients treated with botulinum toxin A injection usually suffers from return of the symptoms which requires successive injections almost every (3-4M)
Rationale for conducting the research:
The concept of adding the zinc supplementation prior to BTXA injection is contributed to the fact that botulinum toxin is a zinc-dependent metalloprotease; therefore, every botulinum toxin molecule must be accompanied with a zinc molecule to effectively paralyze a muscle. However, commercially available BTXA preparations exclude zinc from their preparations, and BTX clinical efficiency and duration varies according to the zinc levels of the patient.
Although the BTX effect could remain for several months, its zinc-dependent proteolytic activity befalls within hours of administration before the toxins are degraded in the tissues.
Therefore, for achieving better results from BTX, the recipients should have adequate zinc levels at the time of administration. Therefore, oral zinc supplement intake prior to BTXA injection may enhance its clinical efficiency and duration.
botulinum neurotoxins are the most potent toxins known. They bind to nerve cells, penetrate the cytosol and block neurotransmitter release. Comparison of their predicted amino acid sequences reveals a highly conserved segment that contains the HExxH zinc binding motif of metalloendo peptidases. The metal content of tetanus toxin was then measured and it was found that one atom of zinc is bound to the light chain of tetanus toxin. Zinc could be reversibly removed by incubation with heavy metal chelators. Zn2+ is coordinated by two histidines with no involvement in cysteines, suggesting that it plays a catalytic rather than a structural role.
Bound Zn + was found to be essential for the tetanus toxin inhibition of neurotransmitter release in Aplysia neurons injected with the light chain. The intracellular activity of the toxin was blocked by phosphoramidon, a very specific inhibitor of zinc endopeptidases. Purified preparations of light chain showed a highly specific proteolytic activity against synaptobrevin, an integral membrane protein of small synaptic vesicles. The present findings indicate that tetanus toxin, and possibly also the botulinum neurotoxins, are metalloproteases and that they block neurotransmitter release via this protease activity. So The use of zinc supplementation prior to BTXA injection has been suggested by several previous studies to prolong its duration of action as well as improve its efficacy
Read the detailed description
Myofascial pain syndrome is a complex disorder of the musculoskeletal system with multifactorial involvement and diverse clinical presentations in several areas of the body It can affect the oro-cranio-facial region, with involvement of the temporomandibular area and masticatory muscles, and is then called myofascial pain dysfunction syndrome.
Botulinum injections can improve blood flow to the muscles and release the nerve fibers compressed by abnormally contracting muscles, both of which may contribute to the cause of pain. In addition, botulinum injections can have an immediate effect owing to direct release of endogenous endorphins from introduction of the needle and alteration in the balance of central neurotransmitters; this is caused by local inhibition of pain peptides from sensory ganglions and nerve terminals, and anti-inflammatory and antiglutaminergic actions . Moreover, studies have shown that 3-10% of patients develop neutralizing antibodies with long-term adverse effects that include muscular atrophy.
BTX clinical efficiency and duration varies according to the zinc levels of the patient.
Although the BTX effect could remain for several months, its zinc-dependent proteolytic activity befalls within hours of administration before the toxins are degraded in the tissues.
Therefore, for achieving better results from BTX, the recipients should have adequate zinc levels at the time of administration. Therefore, oral zinc supplement intake prior to BTXA injection may enhance its clinical efficiency and duration.
Explanation for choice of comparators:
BTX is offered as a solution for myofascial pain patients; nevertheless, it is not considered as a definitive long-term solution so we add the zinc supplementation prior to BTXA injection to increase the clinical duration as reviewed in literature review.
- Conditions
- Myofacial Pain Syndrome, Botulinum Toxin
- Being tested
- Solvazinc 50mg, placebo
- Medical subject headings
- Facial Neuralgia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Solvazinc 50mgDrug
Also called zinc supplement
Patients will receive a daily zinc supplement tablets of 50 mg in the morning after breakfast for 4 days prior to injections.
placeboDrug
placebo
| Study group | Role | What they receive |
|---|---|---|
| first group: (Control group) | Placebo comparator | 1. EMG will be performed for masseter \& temporalis muscles at the diagnosis appointment.
2. Patients will recieve a daily placebo tablet in the morning after breakfast for 4 days prior to injections.
3. Patients will receive a one-time treatment of 50 units of BoNT-A, the dose will be injected into the bilateral masseter muscles (16.7 units each masseter) and 1/3 into the bilateral temporalis (8.3 units each temporalis).
4. Follow up will be performed using EMG for the masseter and temporalis muscles 4 months after the BoNT-A injection. Receives: Drug: placebo |
| second group. (intervention group) | Active comparator | 1. EMG will be performed for masseter \& temporalis muscles at the diagnosis appointment.
2. Patients will receive a daily zinc supplement tablets of 50 mg in the morning after breakfast for 4 days prior to injections.
3. Patients will receive a one-time treatment of 50 units of BoNT-A, the dose will be injected into the bilateral masseter muscles (16.7 units each masseter) and 1/3 into the bilateral temporalis (8.3 units each temporalis).
4. Follow up will be performed using EMG for the masseter and temporalis muscles 4 months after the BoNT-A injection. Receives: Drug: Solvazinc 50mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Muscular Activity
will be assessed by EMG
Measured: 4 months
Pressure Pain Threshold (PPT)
will be assessed by algometer
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2022
- Study start20 May 2022
- Primary completion20 Apr 2023 (estimated)
- Study completion20 May 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Myofacial Pain SyndromeStudies of the same condition, open and under way.
- More trials run by Cairo UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- All patients involved in this study will be divided in to two different groups, one group will undergo zinc supplement then botulinum toxins injection in masseter and temporalis muscle while the other group will have botulinum toxins injection in masseter and temporalis muscle without previous zinc supplement
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cairo University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ahmed Salah Fouad, Cairo University
- Investigators
- Nadia Galal, Study director, professorOmnia Adel aziz, Study director, professor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05605886
- Sponsor's protocol ID
- botox in myofacial pain
- Status last verified
- Feb 2023
- First submitted
- 29 Sep 2022
- Last updated
- 8 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Cohen JL. Scientific skepticism and new discoveries: an analysis of a report of zinc/phytase supplementation and the efficacy of botulinum toxins in treating cosmetic facial rhytides, hemifacial spasm and benign essential blepharospasm. J Cosmet Laser Ther. 2014 Oct;16(5):258-62. doi: 10.3109/14764172.2014.948882. Epub 2014 Sep 2.
PubMed 25105993Lebeda FJ, Cer RZ, Mudunuri U, Stephens R, Singh BR, Adler M. The zinc-dependent protease activity of the botulinum neurotoxins. Toxins (Basel). 2010 May;2(5):978-97. doi: 10.3390/toxins2050978. Epub 2010 May 7.
PubMed 22069621Schiavo G, Poulain B, Rossetto O, Benfenati F, Tauc L, Montecucco C. Tetanus toxin is a zinc protein and its inhibition of neurotransmitter release and protease activity depend on zinc. EMBO J. 1992 Oct;11(10):3577-83. doi: 10.1002/j.1460-2075.1992.tb05441.x.
PubMed 1396558DE LA Torre Canales G, Camara-Souza MB, Poluha RL, Grillo CM, Conti PCR, Sousa MDLR, Rodrigues Garcia RCM, Rizzatti-Barbosa CM. Botulinum toxin type A and acupuncture for masticatory myofascial pain: a randomized clinical trial. J Appl Oral Sci. 2021 Jun 4;29:e20201035. doi: 10.1590/1678-7757-2020-1035. eCollection 2021.
PubMed 34105695
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Botulinum Toxin A in Patients With Myofascial Pain Dysfunction Syndrome With and Without Zinc Supplementation (Randomized Controlled Trial)
- ClinicalTrials.gov ID
- NCT05605886
- Acronym / sponsor ID
- botox in myofacial pain
- Conditions
- Myofacial Pain Syndrome, Botulinum Toxin
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Cairo UniversityUniversity, hospital or other
- Study start
- 20 May 2022 (actual)
- Primary completion
- 20 Apr 2023 (estimated)
- Study completion
- 20 May 2023 (estimated)
- First posted
- 4 Nov 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Research question:
Dose the use of oral zinc supplement improve the effects of botulinum toxins injection in patients with myofascial pain dysfunction syndrome?
Statement of the problem:
MPDS Patients treated with botulinum toxin A injection usually suffers from return of the symptoms which requires successive injections almost every (3-4M)
Rationale for conducting the research:
The concept of adding the zinc supplementation prior to BTXA injection is contributed to the fact that botulinum toxin is a zinc-dependent metalloprotease; therefore, every botulinum toxin molecule must be accompanied with a zinc molecule to effectively paralyze a muscle. However, commercially available BTXA preparations exclude zinc from their preparations, and BTX clinical efficiency and duration varies according to the zinc levels of the patient.
Although the BTX effect could remain for several months, its zinc-dependent proteolytic activity befalls within hours of administration before the toxins are degraded in the tissues.
Therefore, for achieving better results from BTX, the recipients should have adequate zinc levels at the time of administration. Therefore, oral zinc supplement intake prior to BTXA injection may enhance its clinical efficiency and duration.
botulinum neurotoxins are the most potent toxins known. They bind to nerve cells, penetrate the cytosol and block neurotransmitter release. Comparison of their predicted amino acid sequences reveals a highly conserved segment that contains the HExxH zinc binding motif of metalloendo peptidases. The metal content of tetanus toxin was then measured and it was found that one atom of zinc is bound to the light chain of tetanus toxin. Zinc could be reversibly removed by incubation with heavy metal chelators. Zn2+ is coordinated by two histidines with no involvement in cysteines, suggesting that it plays a catalytic rather than a structural role.
Bound Zn + was found to be essential for the tetanus toxin inhibition of neurotransmitter release in Aplysia neurons injected with the light chain. The intracellular activity of the toxin was blocked by phosphoramidon, a very specific inhibitor of zinc endopeptidases. Purified preparations of light chain showed a highly specific proteolytic activity against synaptobrevin, an integral membrane protein of small synaptic vesicles. The present findings indicate that tetanus toxin, and possibly also the botulinum neurotoxins, are metalloproteases and that they block neurotransmitter release via this protease activity. So The use of zinc supplementation prior to BTXA injection has been suggested by several previous studies to prolong its duration of action as well as improve its efficacy
Detailed description
Myofascial pain syndrome is a complex disorder of the musculoskeletal system with multifactorial involvement and diverse clinical presentations in several areas of the body It can affect the oro-cranio-facial region, with involvement of the temporomandibular area and masticatory muscles, and is then called myofascial pain dysfunction syndrome.
Botulinum injections can improve blood flow to the muscles and release the nerve fibers compressed by abnormally contracting muscles, both of which may contribute to the cause of pain. In addition, botulinum injections can have an immediate effect owing to direct release of endogenous endorphins from introduction of the needle and alteration in the balance of central neurotransmitters; this is caused by local inhibition of pain peptides from sensory ganglions and nerve terminals, and anti-inflammatory and antiglutaminergic actions . Moreover, studies have shown that 3-10% of patients develop neutralizing antibodies with long-term adverse effects that include muscular atrophy.
BTX clinical efficiency and duration varies according to the zinc levels of the patient.
Although the BTX effect could remain for several months, its zinc-dependent proteolytic activity befalls within hours of administration before the toxins are degraded in the tissues.
Therefore, for achieving better results from BTX, the recipients should have adequate zinc levels at the time of administration. Therefore, oral zinc supplement intake prior to BTXA injection may enhance its clinical efficiency and duration.
Explanation for choice of comparators:
BTX is offered as a solution for myofascial pain patients; nevertheless, it is not considered as a definitive long-term solution so we add the zinc supplementation prior to BTXA injection to increase the clinical duration as reviewed in literature review.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- All patients involved in this study will be divided in to two different groups, one group will undergo zinc supplement then botulinum toxins injection in masseter and temporalis muscle while the other group will have botulinum toxins injection in masseter and temporalis muscle without previous zinc supplement
| Arm | Type | Receives |
|---|---|---|
| first group: (Control group) | Placebo comparator | Drug: placebo1. EMG will be performed for masseter \& temporalis muscles at the diagnosis appointment. 2. Patients will recieve a daily placebo tablet in the morning after breakfast for 4 days prior to injections. 3. Patients will receive a one-time treatment of 50 units of BoNT-A, the dose will be injected into the bilateral masseter muscles (16.7 units each masseter) and 1/3 into the bilateral temporalis (8.3 units each temporalis). 4. Follow up will be performed using EMG for the masseter and temporalis muscles 4 months after the BoNT-A injection. |
| second group. (intervention group) | Active comparator | Drug: Solvazinc 50mg1. EMG will be performed for masseter \& temporalis muscles at the diagnosis appointment. 2. Patients will receive a daily zinc supplement tablets of 50 mg in the morning after breakfast for 4 days prior to injections. 3. Patients will receive a one-time treatment of 50 units of BoNT-A, the dose will be injected into the bilateral masseter muscles (16.7 units each masseter) and 1/3 into the bilateral temporalis (8.3 units each temporalis). 4. Follow up will be performed using EMG for the masseter and temporalis muscles 4 months after the BoNT-A injection. |
Who may qualify
- Ages
- 17 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- Patients with myofascial pain
- Both genders males and females will be included.
- Ages from 17:50 Y
- General good health
- With complete dentation
Key exclusion criteria (6 listed)
- Subjected to irradiation in the head and neck area less than 1 year ago
- Edentulous patients
- Patient with recent trauma.
- Poor motivation.
- Active infection area related to masseter or temporalis.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Solvazinc 50mgAlso: zinc supplementPatients will receive a daily zinc supplement tablets of 50 mg in the morning after breakfast for 4 days prior to injections. | Drug | second group. (intervention group) |
| placeboplacebo | Drug | first group: (Control group) |
Primary outcome
Muscular Activity
Time frame: 4 months
will be assessed by EMG
Pressure Pain Threshold (PPT)
Time frame: 4 months
will be assessed by algometer
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2023.
- Background: PubMed 25105993Cohen JL. Scientific skepticism and new discoveries: an analysis of a report of zinc/phytase supplementation and the efficacy of botulinum toxins in treating cosmetic facial rhytides, hemifacial spasm and benign essential blepharospasm. J Cosmet Laser Ther. 2014 Oct;16(5):258-62. doi: 10.3109/14764172.2014.948882. Epub 2014 Sep 2.
- Background: PubMed 22069621Lebeda FJ, Cer RZ, Mudunuri U, Stephens R, Singh BR, Adler M. The zinc-dependent protease activity of the botulinum neurotoxins. Toxins (Basel). 2010 May;2(5):978-97. doi: 10.3390/toxins2050978. Epub 2010 May 7.
- Background: PubMed 1396558Schiavo G, Poulain B, Rossetto O, Benfenati F, Tauc L, Montecucco C. Tetanus toxin is a zinc protein and its inhibition of neurotransmitter release and protease activity depend on zinc. EMBO J. 1992 Oct;11(10):3577-83. doi: 10.1002/j.1460-2075.1992.tb05441.x.
- Background: PubMed 34105695DE LA Torre Canales G, Camara-Souza MB, Poluha RL, Grillo CM, Conti PCR, Sousa MDLR, Rodrigues Garcia RCM, Rizzatti-Barbosa CM. Botulinum toxin type A and acupuncture for masticatory myofascial pain: a randomized clinical trial. J Appl Oral Sci. 2021 Jun 4;29:e20201035. doi: 10.1590/1678-7757-2020-1035. eCollection 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nadia Galal study director
professor
Omnia Adel aziz study director
professor
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Solvazinc 50mg in people with Myofacial Pain Syndrome and Botulinum Toxin, run by Cairo University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Muscular Activity (time frame: 4 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05605886, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2023.