Ignite Creation Date:
2024-06-16 @ 11:52 AM
Last Modification Date:
2024-10-26 @ 3:32 PM
Study NCT ID:
NCT06460194
Status:
WITHDRAWN
Last Update Posted:
2024-06-14
First Post:
2019-03-14
Brief Title:
Treatment of Frostbite Sequelae With Botulinum Toxin A
Sponsor:
University Hospital of North Norway
Organization:
University Hospital of North Norway
Study Overview
Official Title:
Botulinum Toxin A in the Treatment of Frostbite Sequelae - a Randomized Double Blind Placebo-controlled Study
Status:
WITHDRAWN
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
No Participants Enrolled
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background Digital vasospasm as part of frostbite sequelae is comparable to the vasospastic disorders found in Raynauds 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
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 Raynauds 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 - 05 cm above a uniformly heated base plate 40 -2C 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 ie 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 1s
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 patients 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
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 - 05 cm above a uniformly heated base plate 40 -2C 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 ie 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 1s
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 patients 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None