Botulinum Toxin Type A for Cold Intolerance Secondary to Digital Amputations and Replantations: A Pilot Study

Study Overview
=================
Brief Summary
-----------------
Patients will be selected for cold intolerance after finger amputation or replantation. They will be given Botox or placebo dose as treatment and assessed over 3 months.

Detailed Description
-----------------
Aim 1: To assess the efficacy of botulinum toxin type A on treating cold intolerance secondary to digital amputations, revascularizations, or replantations Primary null hypothesis: Randomized subjects who receive botulinum toxin type A injections for pain associated with cold intolerance will experience similar changes in pain as compared to patients randomized to receive saline injections (control) • As measured by the Cold Insensitivity and Severity Score (CISS) at one week, four weeks, and twelve weeks Aim 2: To assess the safety of botulinum toxin type A on treating cold intolerance secondary to digital amputations and replantations Hypothesis: Injection of botulinum toxin for cold intolerance secondary to digital amputations and replantations is not associated with any adverse reactions III. SUBJECT SELECTION All adult, English-speaking patients who present with cold intolerance secondary to digital amputation or replantation will be approached and asked to participate in the study. Inclusion criteria Adults (≥18 years) diagnosed with cold intolerance secondary to digital amputations, revascularizations, or replantations and a CISS score of 30 or higher (the threshold for pathological cold intolerance)11 Ability to give informed consent Exclusion criteria Adults ≥ 75 years old Inability or unwillingness to participate in CISS or DASH survey Major medical comorbidity expected to worsen in the next 6 months Comorbid chronic pain condition Severe and untreated mental health conditions or active substance dependence Pregnant or breastfeeding Known hypersensitivity to botulinum toxin Patients with a compromised respiratory function Pre-existing neuromuscular disorders Receiving therapy with aminoglycosides, anticholinergic agents, and muscle relaxants Infection in the proposed injection site All patients who satisfy the inclusion/exclusion criteria will be eligible for enrollment. Vulnerable populations will be excluded from this study. IV. SUBJECT ENROLLMENT A total of twenty-eight patients will be enrolled.

Official Title
-----------------
Botulinum Toxin Type A for Cold Intolerance Secondary to Digital Amputations and Replantations: A Pilot Study

Conditions
-----------------
Cold Intolerance

Intervention / Treatment
-----------------
* Drug: Botulinum toxin type A


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults (≥18 years) diagnosed with cold intolerance secondary to digital amputations, revascularizations, or replantations and a CISS score of 30 or higher (the threshold for pathological cold intolerance)11 Ability to give informed consent Exclusion Criteria: Adults ≥ 75 years old Inability or unwillingness to participate in CISS or DASH survey Major medical comorbidity expected to worsen in the next 6 months Comorbid chronic pain condition Severe and untreated mental health conditions or active substance dependence Pregnant or breastfeeding Known hypersensitivity to botulinum toxin Patients with a compromised respiratory function Pre-existing neuromuscular disorders Receiving therapy with aminoglycosides, anticholinergic agents, and muscle relaxants Infection in the proposed injection site

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Botox<br>The patients in this arm will receive Botox injection to the digital arteries of all affected digits. | Drug: Botulinum toxin type A<br>* Botox injected at digital artery<br>* Other names: Botox;|
| Placebo Comparator: Placebo<br>The patients in this arm will receive placebo injection of saline to the digital arteries of all affected digits. | Drug: Botulinum toxin type A<br>* Botox injected at digital artery<br>* Other names: Botox;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cold Intolerance Severity Score | index of cold intolerance, validated | 3 months | 
| quick dash | a validated measure of hand function | three months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PHQ 9 | depression measure, validated | 3 months |