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

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Cold Intolerance
• Intervention / Treatment: Drug: Botulinum toxin type A

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.

• Study Type: Interventional
• Enrollment (Anticipated): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • MGH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Botox; The patients in this arm will receive Botox injection to the digital arteries of all affected digits.	Drug: Botulinum toxin type A; Botox injected at digital artery; Other Names: Botox
PLACEBO_COMPARATOR: Placebo; The patients in this arm will receive placebo injection of saline to the digital arteries of all affected digits.	Drug: Botulinum toxin type A; Botox injected at digital artery; 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

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Allergan
• Investigators: Principal Investigator: Jonathan M Winograd, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 2, 2021
• Primary Completion (ANTICIPATED): June 2, 2023
• Study Completion (ANTICIPATED): June 2, 2023

Study Registration Dates

• First Submitted: June 2, 2021
• First Submitted That Met QC Criteria: June 2, 2021
• First Posted (ACTUAL): June 8, 2021

Study Record Updates

• Last Update Posted (ACTUAL): August 24, 2022
• Last Update Submitted That Met QC Criteria: August 22, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
• Other Study ID Numbers: 2020P002873

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No