Cold Spray for Insulin-Injection Pain in the Emergency Department

July 24, 2026 updated by: Faruk Danış, MD, Abant Izzet Baysal University

Cold Spray for Pain Reduction During Subcutaneous Insulin Injection in the Emergency Department: A Randomized, Placebo-Controlled, Two-Period Crossover Trial

This randomized, double-blind, placebo-controlled, within-patient crossover trial evaluated whether a vapocoolant (cold) spray applied before subcutaneous insulin injection reduces injection pain compared with a placebo (sterile-water) spray in adults treated in a tertiary-care emergency department. Each participant received a cold spray before one clinically indicated insulin injection and a placebo spray before another, in randomized order, and marked injection pain on a 100-mm visual analog scale 10 seconds after each injection. The within-patient design allowed each participant to serve as their own control.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Adults (>=18 years) receiving subcutaneous insulin in the emergency department and expected to require at least one further subcutaneous insulin injection during the same encounter were allocated 1:1 to one of two treatment sequences using block randomization (block size 4). Sequence 1 received the placebo (sterile-water) spray at the first eligible injection and the cold spray at the next; Sequence 2 received the conditions in reverse order. Allocation was concealed with sequentially numbered, opaque, sealed envelopes. The cold-spray and placebo canisters were identical and over-wrapped in identical opaque covering labeled only as canister number one or canister number two, so that both the participant and the administering clinician were blinded to allocation.

All injections were given in the abdomen (at least 5 cm from the umbilicus, alternating sides) using short-acting regular human insulin (100 IU/mL) at room temperature, administered with a 1-mL single-use syringe and a 25-gauge (0.50 x 25 mm) needle. For the active condition the cold spray was applied to the intended injection area for approximately 10 seconds from approximately 30 cm, and the injection was performed approximately 10 seconds later; the needle was kept in the skin for approximately 10 seconds before withdrawal. The placebo spray was delivered in an identical manner. The insulin dose, the interval between the two injections, and the timing of care followed routine clinical practice and were not standardized by the protocol.

The primary outcome was injection pain measured by each participant on a 100-mm paper visual analog scale (0 = no pain, 100 = worst pain imaginable) 10 seconds after each injection, recorded in millimeters. The primary analysis compared the within-patient VAS difference (cold spray minus placebo) across paired observations, with the validity of the crossover design examined using the standard two-by-two decomposition into carry-over, period, and treatment effects.

Study Type

Interventional

Enrollment (Actual)

100

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Turkey (Türkiye)
      • Bolu, Turkey (Türkiye), 14030
        • Bolu Izzet Baysal Training and Research Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age 18 years or older
  • Receiving subcutaneous insulin in the emergency department
  • Expected to require at least one further subcutaneous insulin injection during the same encounter
  • Able to complete a 100-mm visual analog scale (VAS)

Exclusion Criteria:

  • Allergy to the spray content
  • Local abnormality at the intended abdominal injection site (e.g., active skin infection, hematoma, extensive scarring, or lipohypertrophy)
  • Cognitive condition precluding reliable VAS assessment (e.g., dementia or Alzheimer disease)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Sequence 1: Placebo-first
Placebo (sterile-water) spray before the first eligible subcutaneous insulin injection, then cold (vapocoolant) spray before the next injection.
Other: Cold (vapocoolant) spray
A vapocoolant (cold) spray applied to the intended abdominal injection site for approximately 10 seconds from approximately 30 cm; the subcutaneous insulin injection was performed approximately 10 seconds later, and the needle was kept in the skin for approximately 10 seconds before withdrawal.
Other: Placebo (sterile-water) spray
A sterile-water placebo spray delivered in an identical manner to the active spray (same device handling, distance, and duration) before the subcutaneous insulin injection.
Experimental: Sequence 2: Spray-first
Cold (vapocoolant) spray before the first eligible subcutaneous insulin injection, then placebo (sterile-water) spray before the next injection.
Other: Cold (vapocoolant) spray
A vapocoolant (cold) spray applied to the intended abdominal injection site for approximately 10 seconds from approximately 30 cm; the subcutaneous insulin injection was performed approximately 10 seconds later, and the needle was kept in the skin for approximately 10 seconds before withdrawal.
Other: Placebo (sterile-water) spray
A sterile-water placebo spray delivered in an identical manner to the active spray (same device handling, distance, and duration) before the subcutaneous insulin injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Injection pain on a 100-mm visual analog scale (VAS)
Time Frame: 10 seconds after each injection
Injection pain measured by each participant on a 100-mm paper visual analog scale (0 = no pain, 100 = worst pain imaginable), measured with a ruler and recorded in millimeters. Compared within-patient between the cold-spray and placebo conditions.
10 seconds after each injection

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Abant Izzet Baysal University

Investigators

  • Principal Investigator: Faruk Danis, Abant Izzet Baysal University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 5, 2025

Primary Completion (Actual)

April 1, 2025

Study Completion (Actual)

April 1, 2025

Study Registration Dates

First Submitted

July 22, 2026

First Submitted That Met QC Criteria

July 24, 2026

First Posted (Actual)

July 27, 2026

Study Record Updates

Last Update Posted (Actual)

July 27, 2026

Last Update Submitted That Met QC Criteria

July 24, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BAIBU-EM-2024-386
  • 2024/386 (Other Identifier: Bolu Abant Izzet Baysal University Ethics Committee)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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