Cold HypersensitivityPhase 2NCT06460194
Treatment of Frostbite Sequelae With Botulinum Toxin A
A Phase 2 study testing Botuinum toxin in people with Cold Hypersensitivity and Vascular System Injuries, run by University Hospital of North Norway at 1 site in Norway.
Trial summary
Background Digital vasospasm as part of frostbite sequelae is comparable to the vasospastic disorders found in Raynaud's phenomenon which has been successfully treated with Botulinum toxin type A injections in the palm of the hands. Read more about this study
- Who is it for?
- Ages 20 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Cold Hypersensitivity, Vascular System Injuries, Vibration; Disorder
- What is being tested?
- Botuinum toxin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteNorway
- Study dates
- Nov 2022to 10 Jun 2024
- Phase
- Phase 2
- 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 20 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Inclusion Criteria:- Sequela following 2nd degree frostbite injury in the Norwegian Armed Forces
- Entering the Norwegian Armed Forces Health Registry (NAFHR) between 01.01.2010-31.12.2014
- Still suffering from sequelae related to frostbite injury in their fingers at least four years after their initial frostbite
- Have agreed on receiving a request to participate in the NAFHR quality assurance study.
Exclusion Criteria:- Patients who do not return the signed informed consent form
- Patients who cannot read Norwegian information or answer questions in the study
- Patients who are unable to comply the examination and treatment procedures
- Patients who are unable to travel to University Hospital North Norway in Tromsø for examination and treatment
- Patients who have undergone/is undergoing surgical treatment of hands/fingers
- Patients with known allergy/anaphylaxis in relation to the injection of BTX-A
- Patients who have used/are using drugs that interact with BTX-A injection (anticoagulants)
- Patients who are pregnant before start of the trial and/or during the trial
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Botulinum Toxin A in the Treatment of Frostbite Sequelae - a Randomized, Double Blind, Placebo-controlled Study
Background Digital vasospasm as part of frostbite sequelae is comparable to the vasospastic disorders found in Raynaud's phenomenon which has been successfully treated with Botulinum toxin type A injections in the palm of the hands.
Aim of this pilot study To investigate the effect of Botulinum toxin type A for frostbite sequelae in the fingers.
Read more
Hypothesis The null hypothesis which is that all study-subjects will have equal distribution of symptoms and measurements after treatment, regardless of injection with Botulinum toxin type A or placebo.
Methodology A randomized, double-blind, placebo-controlled study design, The study population consists of four patients with frostbite sequelae. The patients are randomized to either treatment with Botulinum toxin type A or placebo Two patients in the primary treatment group will receive Botulinum toxin type A at their first injection at inclusion, while the two patients in the secondary treatment group will receive normal saline (placebo) as their first injection at inclusion. At 6 weeks follow up, the primary treatment group will receive their second injection of Botulinum toxin type A and the secondary treatment group now will receive their second injection, but this will be their first injection of Botulinum toxin type A.
By using the described study-design, all participating soldiers will get treatment. However, the secondary treatment group will have a delayed onset of treatment with Botulinum toxin type A and serves as a control for the primary treatment group during the initial 6 weeks observation.
Botulinum toxin A and placed will be injected near the neurovascular bundle at the A1 pulley in the palm of the hand using a total dosage 100 U per hand (concentration 50 U per ml), 8-12 U/ injection site.
The effect of Botulinum toxin type A on subjective symptoms will be measured by Patients Subjective Symptom Score (PSSS) The effect of Botulinum toxin type A on peripheral microcirculation will be evaluated with dynamic infrared thermography (DIRT) of the dorsal side of the hands. Quantitative sensory testing will be used to evaluate the effect of Botulinum toxin type A on peripheral nerve function. Both DIRT and QST will be performed prior to the treatment with Botulinum toxin type A and placebo at the start of the pilot study, at 6 weeks as well as 6 weeks after the last injections.
Statistical methods and data analysis will be performed according to the EMA guidelines for biostatistics. Statistical analysis will be performed according to the null hypothesis.
Read the detailed description
Background Frostbite sequelae can have a significant negative impact on quality of life. Depending on the type of frostbite, sequelae such as cold hypersensitivity, sensory loss, chronic pain, hyperhidrosis, growth plate disturbances and osteoarthritis may develop. Long-term paraesthesia with occasional electric shock-type sensations have also been repored. The pathophysiology of these sequelae is still poorly understood although peripheral neurovascular dysfunction plays an important role. This may result in a vasospastic disorder similar as in Raynaud's phenomenon.
Recently, the use of Botulinum toxin type A (BTX-A) for the treatment of vasospastic disorders of the hand has shown to result in great benefits for the patients by reducing the severity and number of vasospastic disorders. BTX-A injections are targeting the neurovascular bundle at or slightly proximal to the A1 pulley in the palm of the hand.
A case history has described the off-label use of BTX-A to treat a Norwegian soldier who suffered from long-term sequelae of frostbite to his hands after a military exercise. He was successfully treated with BTX-A injections in each palm of the hand. At follow up, the patient reported less pain, warmer hands and improved sensory function. Dynamic Infrared thermography (DIRT) showed improved rewarming of all fingers compared to the pre-treatment examination, while Quantattive sensory testing (QST) showed a normalization of sensory function.
Aim of this pilot study To investigate the effect of Botulinum toxin type A for frostbite sequelae in fingers.
Hypothesis The null hypothesis is that all study-subjects will have equal distribution of symptoms and measurements after treatment, regardless of injection with Botulinum toxin type A or placebo.
Methodology A two armed, randomized, double-blind, placebo-controlled study design, performed at one single centre will be used. The study population consists of four soldiers with frostbite sequelae who will be recruited from the Norwegian Armed Forces Health Registry. These four soldiers are randomized to either treatment with Botulinum toxin type A or placebo according to computer-generated random numbers provided by the research unit at the University Hospital of North Norway. Two soldiers in the primary treatment group will receive Botulinum toxin type A at their first injection at inclusion, while the two soldires in the secondary treatment group will receive normal saline (placebo) as their first injection at inclusion. At 6 weeks follow up, the primary treatment group will receive their second injection of Botulinum toxin type A and the secondary treatment group now will receive their second injection, but this will be their first injection of Botulinum toxin type A.
By using the described study-design, all participating soldiers will get treatment. However, the secondary treatment group will have a delayed onset of treatment with Botulinum toxin type A and serves as a control for the primary treatment group during the initial 6 weeks observation.
Botulinum toxin A and placed will be injected near the neurovascular bundle at the A1 pulley in the palm of the hand using a total dosage 100 U per hand (concentration 50 U per ml), 8-12 U/ injection site.
The effect of BTX- A on peripheral microcirculation will be evaluated with dynamic infrared thermography (DIRT) of the dorsal side of the hands. DIRT of the dorsal side of the hands encompass a pre-cooling phase (T1), a cooling phase of one minute (T2), and a four-minute recovery phase (T3, T4, T5 and T6). The pre-cooling phase include baseline measurements before the DIRT takes place and includes also the time from the initial image (T1) until the hands are immersed in water.
The DIRT procedure follows international standards and recommendations involving a cold challenge followed by a rewarming phase with both hands were positioned palms down on a grid made of thin nylon netting strung on a plastic frame. The nylon grid is positioned 7 cm (+/- 0.5 cm) above a uniformly heated base plate (40 +/-2°C) to ensure a thermally uniform background for the thermal imaging.
Quantitative sensory testing will be used to evaluate the effect of BTX- A on peripheral nerve function. Thermal tests will be performed with a device TSA (Medoc, Israel) attaching a thermode to the investigated body part. Thermal tests include detection thresholds for warm and cold sensation, sensory limen (i.e., perception of changing temperatures, pain thresholds for heat and cold pain as well paradoxical cold or heat sensation. It is important to notice, that the maximum temperatures produced by the device are 0° or 50° for cold and warm, respectively. The test system automatically cancels the run, when the participant did not respond with pain up to these temperatures. Mechanical tests include also detection thresholds and pain thresholds. Mechanical detection is evaluated by von Frey hairs (pressure) and a standardized tuning fork (vibration). Pain thresholds are assessed by pin prick stimulation, pressure algometry. Additional tests for allodynia are included as well. Finally, there is a test to assess temporary summation using wind-up ratio to a repeated stimulation with pinprick (10 stimuli with 1/s).
Both DIRT and QST will be performed prior to the treatment with BTX- A and placebo at the start of the pilot study, at 6 weeks as well as 6 weeks after the last injections. At 6 months follow up after the first injection DIRT and QST will be repeated again.
The patient's subjective symptoms are monitored by comparing Patient-Subjective-Symptom-Score (PSSS) after 6 weeks with the baseline values for each patient.
Statistical methods and data analysis will be performed according to the EMA guidelines for biostatistics. Statistical analysis will be performed according to the null hypothesis.
- Conditions
- Cold Hypersensitivity, Vascular System Injuries, Vibration; Disorder, Sensory Disorders, Pain, Nerve
- Being tested
- Botuinum toxin
- Keywords
- cold hypersensitivity, cold intolerance, vasospastic disorder, Raynauds phenomenon, botulinum toxin, infrared thermography, Quantative sensory testing
- Medical subject headings
- Cold Hypersensitivity, Vascular System Injuries, Sensation Disorders, Neuralgia, Raynaud Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Botuinum toxinDrug
Also called Botox
Injection of botulinum toxin in the palm of the hand
| Study group | Role | What they receive |
|---|---|---|
| Botulinum toxin | Active comparator | 100 IU botulinum toxin injection in the palm of the hand Receives: Drug: Botuinum toxin |
| Placebo | Placebo comparator | Saline injection in the palm of the hand Receives: Drug: Botuinum toxin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Subjective symptoms between injection of Botox and placebo at 6 weeks follow up
According to clinical experience, the patient s experience improvement in subjective symptoms after 4-6 weeks follow-up. The patient's subjective symptoms are monitored in a questionnaire of neurological and vasoactive sensations by comparing Patient-Subjective-Symptom-Score (PSSS) wustionnaire after 6 weeks with the baseline values for each patient.
Measured: 6 weeks
Rewarming before and 6 weeks after treatment with Botulinum toxin
According to clinical experience, an improvement is found in the rewarming ability after 4-6 weeks follow-up after injection of Botox. The patients rewarming ability is monitored by comparing the results from Dynamic Infrared Thermography (DIRT) after 6 weeks with the baseline values for each patient.
The DIRT examines the dynamic regulation of peripheral micro-vascularization. Examination of the dorsal side of the hands encompasses a pre-cooling phase (T1), a cooling phase with hands immersed in water for one minute (T2), and a four-minute recovery phase (T3, T4, T5 and T6).
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2024
- Study startNov 2022 (estimated)
- Primary completionJul 2023 (estimated)
- Study completion10 Jun 2024
Why it stopped: No Participants Enrolled.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Cold HypersensitivityStudies of the same condition, open and under way.
- 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
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The methodology uses a two armed, randomized, double-blind, placebo-controlled studydesign, . All participating soldiers will get two injections, one first injection at inclusion and a second injection after 6 weeks. The injections contain either BTX -A or an inert placebo. Both patient and treating doctor is blinded to content of the injection. The two patients in the primary treatment group will receive Botox at their first injection at inclusion, while the two patients in the secondary group will receive placebo as their first injection at inclusion. At 6 weeks follow up, the patients in the primary treatment group will receive their second injection of botox. The patients in the secondary treatment group now will receive their second injection, but this will be their first injection of Botox, given at their 6 weeks follow-up.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital of North Norway
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Arne J Norheim, PhD, Principal investigator, University Hospital of North Norway
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06460194
- Sponsor's protocol ID
- 2018/1961(REK)
- Status last verified
- Jun 2024
- First submitted
- 14 Mar 2019
- Last updated
- 14 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Schaefer G, Huguet J, Zhu SY, Plassmann P, Ring F. Adopting the DICOM standard for medical infrared images. Conf Proc IEEE Eng Med Biol Soc. 2006;2006:236-9. doi: 10.1109/IEMBS.2006.259523.
PubMed 17946389Iorio ML, Masden DL, Higgins JP. Botulinum toxin A treatment of Raynaud's phenomenon: a review. Semin Arthritis Rheum. 2012 Feb;41(4):599-603. doi: 10.1016/j.semarthrit.2011.07.006. Epub 2011 Aug 24.
PubMed 21868066Imray C, Grieve A, Dhillon S; Caudwell Xtreme Everest Research Group. Cold damage to the extremities: frostbite and non-freezing cold injuries. Postgrad Med J. 2009 Sep;85(1007):481-8. doi: 10.1136/pgmj.2008.068635.
PubMed 19734516Fabregat G, De Andres J, Villanueva-Perez VL, Asensio-Samper JM. Subcutaneous and perineural botulinum toxin type a for neuropathic pain: a descriptive review. Clin J Pain. 2013 Nov;29(11):1006-12. doi: 10.1097/AJP.0b013e31827eafff.
PubMed 23370086Norheim AJ, Mercer J, Musial F, de Weerd L. A new treatment for frostbite sequelae; Botulinum toxin. Int J Circumpolar Health. 2017;76(1):1273677. doi: 10.1080/22423982.2016.1273677.
PubMed 28452678Segreto F, Marangi GF, Cerbone V, Persichetti P. The Role of Botulinum Toxin A in the Treatment of Raynaud Phenomenon. Ann Plast Surg. 2016 Sep;77(3):318-23. doi: 10.1097/SAP.0000000000000715.
PubMed 26808752Arnold PB, Campbell CA, Rodeheaver G, Merritt W, Morgan RF, Drake DB. Modification of blood vessel diameter following perivascular application of botulinum toxin-A. Hand (N Y). 2009 Sep;4(3):302-7. doi: 10.1007/s11552-009-9169-8. Epub 2009 Feb 5.
PubMed 19194764Ring EF, Ammer K. Infrared thermal imaging in medicine. Physiol Meas. 2012 Mar;33(3):R33-46. doi: 10.1088/0967-3334/33/3/R33. Epub 2012 Feb 28.
PubMed 22370242Moreira DG, Costello JT, Brito CJ, Adamczyk JG, Ammer K, Bach AJE, Costa CMA, Eglin C, Fernandes AA, Fernandez-Cuevas I, Ferreira JJA, Formenti D, Fournet D, Havenith G, Howell K, Jung A, Kenny GP, Kolosovas-Machuca ES, Maley MJ, Merla A, Pascoe DD, Priego Quesada JI, Schwartz RG, Seixas ARD, Selfe J, Vainer BG, Sillero-Quintana M. Thermographic imaging in sports and exercise medicine: A Delphi study and consensus statement on the measurement of human skin temperature. J Therm Biol. 2017 Oct;69:155-162. doi: 10.1016/j.jtherbio.2017.07.006. Epub 2017 Jul 18.
PubMed 29037377Maier C, Baron R, Tolle TR, Binder A, Birbaumer N, Birklein F, Gierthmuhlen J, Flor H, Geber C, Huge V, Krumova EK, Landwehrmeyer GB, Magerl W, Maihofner C, Richter H, Rolke R, Scherens A, Schwarz A, Sommer C, Tronnier V, Uceyler N, Valet M, Wasner G, Treede DR. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): somatosensory abnormalities in 1236 patients with different neuropathic pain syndromes. Pain. 2010 Sep;150(3):439-450. doi: 10.1016/j.pain.2010.05.002.
PubMed 20627413Aru RG, Songcharoen SJ, Seals SR, Arnold PB, Hester RL. Microcirculatory Effects of Botulinum Toxin A in the Rat: Acute and Chronic Vasodilation. Ann Plast Surg. 2017 Jul;79(1):82-85. doi: 10.1097/SAP.0000000000001054.
PubMed 28509693
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Botulinum Toxin A in the Treatment of Frostbite Sequelae - a Randomized, Double Blind, Placebo-controlled Study
- ClinicalTrials.gov ID
- NCT06460194
- Acronym / sponsor ID
- 2018/1961(REK)
- Conditions
- Cold Hypersensitivity, Vascular System Injuries, Vibration; Disorder, Sensory Disorders, Pain, Nerve
- Keywords
- cold hypersensitivity, cold intolerance, vasospastic disorder, Raynauds phenomenon, botulinum toxin, infrared thermography, Quantative sensory testing
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No Participants Enrolled.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University Hospital of North NorwayUniversity, hospital or other
- Study start
- Nov 2022 (estimated)
- Primary completion
- Jul 2023 (estimated)
- Study completion
- 10 Jun 2024 (actual)
- First posted
- 14 Jun 2024 (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.
Background Digital vasospasm as part of frostbite sequelae is comparable to the vasospastic disorders found in Raynaud's phenomenon which has been successfully treated with Botulinum toxin type A injections in the palm of the hands.
Aim of this pilot study To investigate the effect of Botulinum toxin type A for frostbite sequelae in the fingers.
Hypothesis The null hypothesis which is that all study-subjects will have equal distribution of symptoms and measurements after treatment, regardless of injection with Botulinum toxin type A or placebo.
Methodology A randomized, double-blind, placebo-controlled study design, The study population consists of four patients with frostbite sequelae. The patients are randomized to either treatment with Botulinum toxin type A or placebo Two patients in the primary treatment group will receive Botulinum toxin type A at their first injection at inclusion, while the two patients in the secondary treatment group will receive normal saline (placebo) as their first injection at inclusion. At 6 weeks follow up, the primary treatment group will receive their second injection of Botulinum toxin type A and the secondary treatment group now will receive their second injection, but this will be their first injection of Botulinum toxin type A.
By using the described study-design, all participating soldiers will get treatment. However, the secondary treatment group will have a delayed onset of treatment with Botulinum toxin type A and serves as a control for the primary treatment group during the initial 6 weeks observation.
Botulinum toxin A and placed will be injected near the neurovascular bundle at the A1 pulley in the palm of the hand using a total dosage 100 U per hand (concentration 50 U per ml), 8-12 U/ injection site.
The effect of Botulinum toxin type A on subjective symptoms will be measured by Patients Subjective Symptom Score (PSSS) The effect of Botulinum toxin type A on peripheral microcirculation will be evaluated with dynamic infrared thermography (DIRT) of the dorsal side of the hands. Quantitative sensory testing will be used to evaluate the effect of Botulinum toxin type A on peripheral nerve function. Both DIRT and QST will be performed prior to the treatment with Botulinum toxin type A and placebo at the start of the pilot study, at 6 weeks as well as 6 weeks after the last injections.
Statistical methods and data analysis will be performed according to the EMA guidelines for biostatistics. Statistical analysis will be performed according to the null hypothesis.
Detailed description
Background Frostbite sequelae can have a significant negative impact on quality of life. Depending on the type of frostbite, sequelae such as cold hypersensitivity, sensory loss, chronic pain, hyperhidrosis, growth plate disturbances and osteoarthritis may develop. Long-term paraesthesia with occasional electric shock-type sensations have also been repored. The pathophysiology of these sequelae is still poorly understood although peripheral neurovascular dysfunction plays an important role. This may result in a vasospastic disorder similar as in Raynaud's phenomenon.
Recently, the use of Botulinum toxin type A (BTX-A) for the treatment of vasospastic disorders of the hand has shown to result in great benefits for the patients by reducing the severity and number of vasospastic disorders. BTX-A injections are targeting the neurovascular bundle at or slightly proximal to the A1 pulley in the palm of the hand.
A case history has described the off-label use of BTX-A to treat a Norwegian soldier who suffered from long-term sequelae of frostbite to his hands after a military exercise. He was successfully treated with BTX-A injections in each palm of the hand. At follow up, the patient reported less pain, warmer hands and improved sensory function. Dynamic Infrared thermography (DIRT) showed improved rewarming of all fingers compared to the pre-treatment examination, while Quantattive sensory testing (QST) showed a normalization of sensory function.
Aim of this pilot study To investigate the effect of Botulinum toxin type A for frostbite sequelae in fingers.
Hypothesis The null hypothesis is that all study-subjects will have equal distribution of symptoms and measurements after treatment, regardless of injection with Botulinum toxin type A or placebo.
Methodology A two armed, randomized, double-blind, placebo-controlled study design, performed at one single centre will be used. The study population consists of four soldiers with frostbite sequelae who will be recruited from the Norwegian Armed Forces Health Registry. These four soldiers are randomized to either treatment with Botulinum toxin type A or placebo according to computer-generated random numbers provided by the research unit at the University Hospital of North Norway. Two soldiers in the primary treatment group will receive Botulinum toxin type A at their first injection at inclusion, while the two soldires in the secondary treatment group will receive normal saline (placebo) as their first injection at inclusion. At 6 weeks follow up, the primary treatment group will receive their second injection of Botulinum toxin type A and the secondary treatment group now will receive their second injection, but this will be their first injection of Botulinum toxin type A.
By using the described study-design, all participating soldiers will get treatment. However, the secondary treatment group will have a delayed onset of treatment with Botulinum toxin type A and serves as a control for the primary treatment group during the initial 6 weeks observation.
Botulinum toxin A and placed will be injected near the neurovascular bundle at the A1 pulley in the palm of the hand using a total dosage 100 U per hand (concentration 50 U per ml), 8-12 U/ injection site.
The effect of BTX- A on peripheral microcirculation will be evaluated with dynamic infrared thermography (DIRT) of the dorsal side of the hands. DIRT of the dorsal side of the hands encompass a pre-cooling phase (T1), a cooling phase of one minute (T2), and a four-minute recovery phase (T3, T4, T5 and T6). The pre-cooling phase include baseline measurements before the DIRT takes place and includes also the time from the initial image (T1) until the hands are immersed in water.
The DIRT procedure follows international standards and recommendations involving a cold challenge followed by a rewarming phase with both hands were positioned palms down on a grid made of thin nylon netting strung on a plastic frame. The nylon grid is positioned 7 cm (+/- 0.5 cm) above a uniformly heated base plate (40 +/-2°C) to ensure a thermally uniform background for the thermal imaging.
Quantitative sensory testing will be used to evaluate the effect of BTX- A on peripheral nerve function. Thermal tests will be performed with a device TSA (Medoc, Israel) attaching a thermode to the investigated body part. Thermal tests include detection thresholds for warm and cold sensation, sensory limen (i.e., perception of changing temperatures, pain thresholds for heat and cold pain as well paradoxical cold or heat sensation. It is important to notice, that the maximum temperatures produced by the device are 0° or 50° for cold and warm, respectively. The test system automatically cancels the run, when the participant did not respond with pain up to these temperatures. Mechanical tests include also detection thresholds and pain thresholds. Mechanical detection is evaluated by von Frey hairs (pressure) and a standardized tuning fork (vibration). Pain thresholds are assessed by pin prick stimulation, pressure algometry. Additional tests for allodynia are included as well. Finally, there is a test to assess temporary summation using wind-up ratio to a repeated stimulation with pinprick (10 stimuli with 1/s).
Both DIRT and QST will be performed prior to the treatment with BTX- A and placebo at the start of the pilot study, at 6 weeks as well as 6 weeks after the last injections. At 6 months follow up after the first injection DIRT and QST will be repeated again.
The patient's subjective symptoms are monitored by comparing Patient-Subjective-Symptom-Score (PSSS) after 6 weeks with the baseline values for each patient.
Statistical methods and data analysis will be performed according to the EMA guidelines for biostatistics. Statistical analysis will be performed according to the null hypothesis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- The methodology uses a two armed, randomized, double-blind, placebo-controlled studydesign, . All participating soldiers will get two injections, one first injection at inclusion and a second injection after 6 weeks. The injections contain either BTX -A or an inert placebo. Both patient and treating doctor is blinded to content of the injection. The two patients in the primary treatment group will receive Botox at their first injection at inclusion, while the two patients in the secondary group will receive placebo as their first injection at inclusion. At 6 weeks follow up, the patients in the primary treatment group will receive their second injection of botox. The patients in the secondary treatment group now will receive their second injection, but this will be their first injection of Botox, given at their 6 weeks follow-up.
| Arm | Type | Receives |
|---|---|---|
| Botulinum toxin | Active comparator | Drug: Botuinum toxin100 IU botulinum toxin injection in the palm of the hand |
| Placebo | Placebo comparator | Drug: Botuinum toxinSaline injection in the palm of the hand |
Who may qualify
- Ages
- 20 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| Botuinum toxinAlso: BotoxInjection of botulinum toxin in the palm of the hand | Drug | Botulinum toxin, Placebo |
Primary outcome
Subjective symptoms between injection of Botox and placebo at 6 weeks follow up
Time frame: 6 weeks
According to clinical experience, the patient s experience improvement in subjective symptoms after 4-6 weeks follow-up. The patient's subjective symptoms are monitored in a questionnaire of neurological and vasoactive sensations by comparing Patient-Subjective-Symptom-Score (PSSS) wustionnaire after 6 weeks with the baseline values for each patient.
Rewarming before and 6 weeks after treatment with Botulinum toxin
Time frame: 6 weeks
According to clinical experience, an improvement is found in the rewarming ability after 4-6 weeks follow-up after injection of Botox. The patients rewarming ability is monitored by comparing the results from Dynamic Infrared Thermography (DIRT) after 6 weeks with the baseline values for each patient. The DIRT examines the dynamic regulation of peripheral micro-vascularization. Examination of the dorsal side of the hands encompasses a pre-cooling phase (T1), a cooling phase with hands immersed in water for one minute (T2), and a four-minute recovery phase (T3, T4, T5 and T6).
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2024.
- Background: PubMed 17946389Schaefer G, Huguet J, Zhu SY, Plassmann P, Ring F. Adopting the DICOM standard for medical infrared images. Conf Proc IEEE Eng Med Biol Soc. 2006;2006:236-9. doi: 10.1109/IEMBS.2006.259523.
- Results publication: PubMed 21868066Iorio ML, Masden DL, Higgins JP. Botulinum toxin A treatment of Raynaud's phenomenon: a review. Semin Arthritis Rheum. 2012 Feb;41(4):599-603. doi: 10.1016/j.semarthrit.2011.07.006. Epub 2011 Aug 24.
- Results publication: PubMed 19734516Imray C, Grieve A, Dhillon S; Caudwell Xtreme Everest Research Group. Cold damage to the extremities: frostbite and non-freezing cold injuries. Postgrad Med J. 2009 Sep;85(1007):481-8. doi: 10.1136/pgmj.2008.068635.
- Results publication: PubMed 23370086Fabregat G, De Andres J, Villanueva-Perez VL, Asensio-Samper JM. Subcutaneous and perineural botulinum toxin type a for neuropathic pain: a descriptive review. Clin J Pain. 2013 Nov;29(11):1006-12. doi: 10.1097/AJP.0b013e31827eafff.
- Results publication: PubMed 28452678Norheim AJ, Mercer J, Musial F, de Weerd L. A new treatment for frostbite sequelae; Botulinum toxin. Int J Circumpolar Health. 2017;76(1):1273677. doi: 10.1080/22423982.2016.1273677.
- Results publication: PubMed 26808752Segreto F, Marangi GF, Cerbone V, Persichetti P. The Role of Botulinum Toxin A in the Treatment of Raynaud Phenomenon. Ann Plast Surg. 2016 Sep;77(3):318-23. doi: 10.1097/SAP.0000000000000715.
- Results publication: PubMed 19194764Arnold PB, Campbell CA, Rodeheaver G, Merritt W, Morgan RF, Drake DB. Modification of blood vessel diameter following perivascular application of botulinum toxin-A. Hand (N Y). 2009 Sep;4(3):302-7. doi: 10.1007/s11552-009-9169-8. Epub 2009 Feb 5.
- Results publication: PubMed 22370242Ring EF, Ammer K. Infrared thermal imaging in medicine. Physiol Meas. 2012 Mar;33(3):R33-46. doi: 10.1088/0967-3334/33/3/R33. Epub 2012 Feb 28.
- Results publication: PubMed 29037377Moreira DG, Costello JT, Brito CJ, Adamczyk JG, Ammer K, Bach AJE, Costa CMA, Eglin C, Fernandes AA, Fernandez-Cuevas I, Ferreira JJA, Formenti D, Fournet D, Havenith G, Howell K, Jung A, Kenny GP, Kolosovas-Machuca ES, Maley MJ, Merla A, Pascoe DD, Priego Quesada JI, Schwartz RG, Seixas ARD, Selfe J, Vainer BG, Sillero-Quintana M. Thermographic imaging in sports and exercise medicine: A Delphi study and consensus statement on the measurement of human skin temperature. J Therm Biol. 2017 Oct;69:155-162. doi: 10.1016/j.jtherbio.2017.07.006. Epub 2017 Jul 18.
- Results publication: PubMed 20627413Maier C, Baron R, Tolle TR, Binder A, Birbaumer N, Birklein F, Gierthmuhlen J, Flor H, Geber C, Huge V, Krumova EK, Landwehrmeyer GB, Magerl W, Maihofner C, Richter H, Rolke R, Scherens A, Schwarz A, Sommer C, Tronnier V, Uceyler N, Valet M, Wasner G, Treede DR. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): somatosensory abnormalities in 1236 patients with different neuropathic pain syndromes. Pain. 2010 Sep;150(3):439-450. doi: 10.1016/j.pain.2010.05.002.
- Results publication: PubMed 28509693Aru RG, Songcharoen SJ, Seals SR, Arnold PB, Hester RL. Microcirculatory Effects of Botulinum Toxin A in the Rat: Acute and Chronic Vasodilation. Ann Plast Surg. 2017 Jul;79(1):82-85. doi: 10.1097/SAP.0000000000001054.
- Individual participant dataSharing planned: Undecided
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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.
Arne J Norheim, PhD principal investigator
University Hospital of North Norway
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Botuinum toxin in people with Cold Hypersensitivity and Vascular System Injuries, run by University Hospital of North Norway at 1 site in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: withdrawn, as of the sponsor's last update on 14 Jun 2024. 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 Norway. 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?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Subjective symptoms between injection of Botox and placebo at 6 weeks follow up (time frame: 6 weeks). 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 NCT06460194, which also lists 11 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 14 Jun 2024.