Local Anesthetic Response in Ehlers-Danlos Syndrome (EDS) and Healthy Volunteers

Local anesthetic resistance is commonly reported by patients with EDS. However, there are no objective data on the occurrence of local anesthetic resistance in EDS patients and in healthy volunteers. We propose to collect such objective data on the frequency of drug resistance and whether any problems with local anesthesia are due to initial ineffectiveness or due to its effects dissipating too soon.

Study Overview

• Status: Active, not recruiting
• Conditions: Anesthesia, Local; Ehlers-Danlos Syndrome
• Intervention / Treatment: Drug: 0.9% Sodium Chloride Injection; Drug: Lidocaine Injection 2%; Drug: Bupivacaine Injection 0.5%

Detailed Description

There was a prior large online questionnaire to better understand the issues around local anesthetic resistance. By November 2018, 933 EDS patients (total 1059 respondents) completed the survey, 99.2% of which had previously received local anesthetics. Among these patients, 88% reported that they have "had a problem with local anesthetic injection not working adequately or properly," while only 54% of respondents without EDS reported a similar problem. These data suggests that local anesthetic resistance might be more prevalent in patients with EDS than in the general population. If these findings are true, then this might have significant implications for the appropriate management of these patients during minor surgery and dental procedures.

This study aims to assess the frequency and related issues around local anesthetic resistance in EDS patients, including whether the problem is a lack of analgesia or a timing effect (short duration of action or delayed onset of action), and whether the problem relates only to some local anesthetics or whether there is a problem with the whole class of local anesthetics.

• Study Type: Observational
• Enrollment (Estimated): 230

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

EDS patients and non-EDS participants

Description

Inclusion Criteria:

• EDS patients, clinically diagnosed hypermobile EDS based on 2017 criteria
• EDS patients with genetically proven non-hypermobile EDS
• Healthy participants, no EDS
• Able and willing to provide informed consent

Exclusion Criteria:

• Known allergy to Lidocaine or Bupivacaine
• Unable to provide informed consent

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
EDS Patients; Patients meeting the diagnostic criteria (2017) for Ehlers-Danlos Syndrome	Drug: 0.9% Sodium Chloride Injection; All participants will be injected subcutaneously with a single 0.5ml dose; Other Names: Saline; Drug: Lidocaine Injection 2%; All participants will be injected subcutaneously with a single 0.5ml dose; Other Names: Xylocaine; lignocaine; Drug: Bupivacaine Injection 0.5%; All participants will be injected subcutaneously with a single 0.5ml dose; Other Names: marcaine
Healthy Volunteers; Healthy control volunteers who do not meet the criteria for Ehlers-Danlos Syndrome	Drug: 0.9% Sodium Chloride Injection; All participants will be injected subcutaneously with a single 0.5ml dose; Other Names: Saline; Drug: Lidocaine Injection 2%; All participants will be injected subcutaneously with a single 0.5ml dose; Other Names: Xylocaine; lignocaine; Drug: Bupivacaine Injection 0.5%; All participants will be injected subcutaneously with a single 0.5ml dose; Other Names: marcaine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delta Pain Scores Lidocaine at 5 min	Difference between the pain score at the Lidocaine injection locations (compared to a control location) and the saline injection location (compared to a control location). The pain scale is .a 4 level scale from 0 ("absent sensation"), to 1 ("dull pressure"), to 2 ("sharp but less than a control [non-injected] region) to 3 (same or worse than the control region).	5 minutes post-injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delta Pain Scores Lidocaine at 30 min	Difference between the pain score at the Lidocaine injection locations (compared to a control location) and the saline injection location (compared to a control location). The pain scale is .a 4 level scale from 0 ("absent sensation"), to 1 ("dull pressure"), to 2 ("sharp but less than a control [non-injected] region) to 3 (same or worse than the control region).	30 min
Delta Pain Scores Bupivacaine at 5 min	Difference between the pain score at the bupivacaine injection locations (compared to a control location) and the saline injection location (compared to a control location). The pain scale is .a 4 level scale from 0 ("absent sensation"), to 1 ("dull pressure"), to 2 ("sharp but less than a control [non-injected] region) to 3 (same or worse than the control region).	5 min
Delta Pain Scores Bupivacaine at 30 min	Difference between the pain score at the bupivacaine injection locations (compared to a control location) and the saline injection location (compared to a control location). The pain scale is .a 4 level scale from 0 ("absent sensation"), to 1 ("dull pressure"), to 2 ("sharp but less than a control [non-injected] region) to 3 (same or worse than the control region).	30 min

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: University of Calgary
• Investigators: Principal Investigator: Satish R Raj, MD MSCI, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2019
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: July 25, 2019
• First Submitted That Met QC Criteria: July 25, 2019
• First Posted (Actual): July 29, 2019

Study Record Updates

• Last Update Posted (Estimated): October 14, 2025
• Last Update Submitted That Met QC Criteria: October 8, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Ehlers-Danlos Syndrome; Local Anesthesia Resistance
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Connective Tissue Diseases; Hematologic Diseases; Skin Diseases; Congenital Abnormalities; Hemostatic Disorders; Hemorrhagic Disorders; Skin Diseases, Genetic; Skin Abnormalities; Collagen Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin and Connective Tissue Diseases; Hemic and Lymphatic Diseases; Ehlers-Danlos Syndrome; Organic Chemicals; Anilides; Amides; Aniline Compounds; Amines; Acetanilides; Inorganic Chemicals; Chlorine Compounds; Sodium Compounds; Chlorides; Hydrochloric Acid; Bupivacaine; Lidocaine; Sodium Chloride
• Other Study ID Numbers: 190957

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