Pain
Conditions
Keywords
fingerstick, opioid, heelstick, loperamide, topical opioid
Brief summary
This study evaluates topical loperamide 5% gel in reducing pain during repeat finger lancing (finger stick) in healthy adults. Half of participants received 5% loperamide gel applied to their fingertip prior to their second lance and the other half received the gel only.
Detailed description
Lancing the finger and heel to obtain capillary blood for specimen collection and diagnostic testing is a painful and tissue damaging procedure. With each lance, there is direct splicing of capillaries along with free nerve endings resulting in an immediate localized pain response and hyperalgesia from the release of pain producing substances. Opioid agonists (morphine, fentanyl, loperamide) have demonstrated significant analgesia when locally injected or topically applied to a site of inflammation/injury in animal models. Loperamide, a piperdine derivative with a structure similar to the synthetic opioid meperidine, has strong affinity for Mu opioid receptors. It was approved by the FDA in 1969 as an anti-diarrheal agent with Mu opioid activity mimicked the constipating effects of other opioids, but with markedly reduced CNS effects due to its affinity for p-glycoprotein, preventing crossing the blood brain barrier (BBB) under normal circumstances. This prospective, double-blind, repeated measures, randomized investigational new drug trial used loperamide developed as a topical gel in 34 adult participants to determine its analgesic effects during repeat finger lancing. The investigators also assessed for any local skin reaction to the gel application and for any constipation or abdominal cramping which might be evidence of systemic absorption and Mu opioid agonist activity on the gut. This study would be applicable for use in 28.9 million adults who are diabetic and require finger lancing for blood glucose monitoring and the high risk newborn population who require repeat heel lancing for specimen collection.
Interventions
DRUGLoperamide
Following lance one, 0.2 grams of loperamide 5% gel was applied from a sterile syringe to the participants previous lance site within an 8 mm diameter circular plastic mold. The loperamide gel was rubbed lightly on the skin surface for one minute using a gloved finger swirled into the mold site. The mold was removed and the site was covered with a transparent occlusive dressing for 30 minutes. At 30 minutes the gel was removed with gauze, the skin cleaned with an alcohol wipe and the second lance was done within the same location as the first. The loperamide gel was also swabbed to the forearm within the 8 mm mold and left in place for 30 minutes.
DRUGDrug, placebo gel
Following lance one, 0.2 grams of gel alone was applied to the participants previous lance site within an 8mm diameter circular plastic mold. The gel was rubbed lightly on the skin surface for one minute using a gloved finger swirled into the mold site. The mold was removed and the site was covered with a transparent occlusive dressing left in place for 30 minutes. At 30 minutes the gel was removed with gauze, the skin cleaned with an alcohol wipe and the second lance was done within the same location as the first. The placebo gel was also swabbed to the forearm within the 8 mm mold and left in place for 30 minutes.
Sponsors
Rush University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy volunteers willing to have 2 consecutive finger sticks completed.
Exclusion criteria
* Participants are excluded if they have a history of drug induced hypersensitivity reactions; took any anti-inflammatory medications in the past 12 hours; if they routinely performed finger lancing for blood specimen monitoring (e.g. diabetes); or had calloused fingers pads.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain - Numeric Rating Scale | Within one minute following each lance | Subject responded to Please mark the degree of pain you felt following the lance and drew a line on a 0 (no pain) to 10 (worst possible pain) scale within one minute of the lance. |
| Pain - Comparative Pain Scale | Within one minute of the second lance, participants will be asked to circle their comparison pain rating to the first lance delivered 40 minutes earlier to the same digit. | Within one minute following the second lance, subjects were asked In comparison to the first finger stick, how would you rate the pain of the second: much less, a little less, about the same, a little more or much more. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Beats Per Minute (BPM) Within Groups During Lance One and Lance Two Procedure | Average of BPM during each phase of the lance procedure (lance, specimen collection, recovery) | BPM obtained using the Kenek Edge Pulse Oximeter System using a flipclop sensor and companion app. Mean BPM during lance initiation through recovery (30 seconds following lance) reported. |
| 24 Hour Numeric Pain (0 to 10 Scale) in the Lanced Finger Site. | 24 hours following the second lance. | Numeric pain rating using the numeric rating scale 0-10 (0=no pain and 10 = worst pain ever) at 24 hours following finger lancing |
| Safety - Number of Participants With Treatment Related Adverse Gastrointestinal Disorders Using the CTCAE V. 4 With Focus on Abdominal Pain, Constipation and Diarrhea | 24 hour participant report | Participant report of any abdominal pain or change in stool pattern (constipation or diarrhea) over the past 24 hours using the CTCAE V.4 with focus on abdominal pain, constipation and diarrhea.. |
| Safety- Number of Participants With Treatment Related Adverse Events as Assessed by the CTCAE V.4 | Direct observation of treatment site at one minute and 30 minutes. Participant report at 24 hours if any redness is present on the forearm. | CTCAE will be utilized for reporting any adverse events with specific focus on skin and tissue disorders. A Standard erythema scale (0=no effect, 0.5=observer indecisive, 1=faint pink-no border, 1.5=faint pink border, 2=faint pink with one border, 2.5=fain pink with two borders, 3=red, 3.5=fiery red 4=violaceous red will also be used to classify skin erythema. |
| 24 Hour Sensitivity in Lanced Finger to Touch and Pressure | 24 hours post lancing. | Sensitivity questions adapted from the pain quality assessment scale: After the application of the gel in both the treatment and control (Placebo) group, each participant from both groups was asked about the sensitivity of the fingerstick site to light or clothing rubbing against it over the past day (24 hours later), the sensitivity scale is as follows: (0=non-sensitive; 1-sensitive). A scale score of 0 means- a better outcome. After the application of the gel in both the treatment and control (Placebo) group, each participant from both groups was asked about the sensitivity of the fingerstick site when something was pressed against it over the past day (24 hours later), the sensitivity scale is as follows: (0=not tender and 1=tender). A scale score of 0 means- a better outcome. |
Participant flow
Pre-assignment details
Individuals were excluded from participating if they had a history of drug induced hypersensitivity reactions; took any anti-inflammatory medications in the past 12 hours; if they routinely performed finger lancing for blood specimen monitoring (e.g. diabetes); or had calloused fingers pads.
Participants by arm
| Arm | Count |
|---|---|
| 5% Loperamide Gel Loperamide: Following lance one, 0.2 grams of loperamide 5% gel was applied from a sterile syringe to the participants previous lance site within an 8 mm diameter circular plastic mold. The loperamide gel was rubbed lightly on the skin surface for one minute using a gloved finger swirled into the mold site. The mold was removed and the site was covered with a transparent occlusive dressing for 30 minutes. At 30 minutes the gel was removed with gauze, the skin cleaned with an alcohol wipe and the second lance was done within the same location as the first. The loperamide gel was also swabbed to the forearm within the 8 mm mold and left in place for 30 minutes. | 17 |
| Placebo Gel Drug, placebo gel: Following lance one, 0.2 grams of gel alone was applied to the participants previous lance site within an 8mm diameter circular plastic mold. The gel was rubbed lightly on the skin surface for one minute using a gloved finger swirled into the mold site. The mold was removed and the site was covered with a transparent occlusive dressing left in place for 30 minutes. At 30 minutes the gel was removed with gauze, the skin cleaned with an alcohol wipe and the second lance was done within the same location as the first. The placebo gel was also swabbed to the forearm within the 8 mm mold and left in place for 30 minutes. | 17 |
| Total | 34 |
Baseline characteristics
| Characteristic | 5% Loperamide Gel | Placebo Gel | Total |
|---|---|---|---|
| Age, Continuous | 42 years | 39 years | 41.5 years |
| Anxiety to needle stick scale | 2.8 units on a scale STANDARD_DEVIATION 2.6 | 3.2 units on a scale STANDARD_DEVIATION 2.6 | 2.9 units on a scale STANDARD_DEVIATION 2.5 |
| Region of Enrollment United States | 17 participants | 17 participants | 34 participants |
| Sex: Female, Male Female | 12 Participants | 12 Participants | 24 Participants |
| Sex: Female, Male Male | 5 Participants | 5 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 17 | 0 / 17 |
| serious Total, serious adverse events | 0 / 17 | 0 / 17 |
Outcome results
Primary
Pain - Comparative Pain Scale
Within one minute following the second lance, subjects were asked In comparison to the first finger stick, how would you rate the pain of the second: much less, a little less, about the same, a little more or much more.
Time frame: Within one minute of the second lance, participants will be asked to circle their comparison pain rating to the first lance delivered 40 minutes earlier to the same digit.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pain Rating Loperamide Study Arm | Pain - Comparative Pain Scale | Participants rating pain a little less | 5 Participants |
| Pain Rating Loperamide Study Arm | Pain - Comparative Pain Scale | Participants rating pain much more | 1 Participants |
| Pain Rating Loperamide Study Arm | Pain - Comparative Pain Scale | Participants rating pain a little more | 1 Participants |
| Pain Rating Loperamide Study Arm | Pain - Comparative Pain Scale | Participants rating pain about the same | 7 Participants |
| Pain Rating Loperamide Study Arm | Pain - Comparative Pain Scale | Participants rating pain much less | 3 Participants |
| Pain Rating Placebo Study Arm | Pain - Comparative Pain Scale | Participants rating pain about the same | 9 Participants |
| Pain Rating Placebo Study Arm | Pain - Comparative Pain Scale | Participants rating pain much less | 0 Participants |
| Pain Rating Placebo Study Arm | Pain - Comparative Pain Scale | Participants rating pain a little less | 0 Participants |
| Pain Rating Placebo Study Arm | Pain - Comparative Pain Scale | Participants rating pain a little more | 4 Participants |
| Pain Rating Placebo Study Arm | Pain - Comparative Pain Scale | Participants rating pain much more | 4 Participants |
Primary
Pain - Numeric Rating Scale
Subject responded to Please mark the degree of pain you felt following the lance and drew a line on a 0 (no pain) to 10 (worst possible pain) scale within one minute of the lance.
Time frame: Within one minute following each lance
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pain Rating Loperamide Study Arm | Pain - Numeric Rating Scale | Basal Lance | 2.6 units on a scale | Standard Deviation 1.7 |
| Pain Rating Loperamide Study Arm | Pain - Numeric Rating Scale | Lance 2 | 1.9 units on a scale | Standard Deviation 1.4 |
| Pain Rating Placebo Study Arm | Pain - Numeric Rating Scale | Basal Lance | 2.5 units on a scale | Standard Deviation 2.3 |
| Pain Rating Placebo Study Arm | Pain - Numeric Rating Scale | Lance 2 | 4.2 units on a scale | Standard Deviation 2.4 |
p-value: 0.8Paired Sample T-test
p-value: 0.003Paired Sample T-test
p-value: 0.002t-test, 2 sided
Secondary
24 Hour Numeric Pain (0 to 10 Scale) in the Lanced Finger Site.
Numeric pain rating using the numeric rating scale 0-10 (0=no pain and 10 = worst pain ever) at 24 hours following finger lancing
Time frame: 24 hours following the second lance.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pain Rating Loperamide Study Arm | 24 Hour Numeric Pain (0 to 10 Scale) in the Lanced Finger Site. | .23 score on a scale | Standard Deviation 0.56 |
| Pain Rating Placebo Study Arm | 24 Hour Numeric Pain (0 to 10 Scale) in the Lanced Finger Site. | 1.23 score on a scale | Standard Deviation 1.4 |
p-value: 0.01t-test, 1 sided
p-value: 0.001Chi-squared
Secondary
24 Hour Sensitivity in Lanced Finger to Touch and Pressure
Sensitivity questions adapted from the pain quality assessment scale: After the application of the gel in both the treatment and control (Placebo) group, each participant from both groups was asked about the sensitivity of the fingerstick site to light or clothing rubbing against it over the past day (24 hours later), the sensitivity scale is as follows: (0=non-sensitive; 1-sensitive). A scale score of 0 means- a better outcome. After the application of the gel in both the treatment and control (Placebo) group, each participant from both groups was asked about the sensitivity of the fingerstick site when something was pressed against it over the past day (24 hours later), the sensitivity scale is as follows: (0=not tender and 1=tender). A scale score of 0 means- a better outcome.
Time frame: 24 hours post lancing.
Population: 17 participants from both groups/arms were analyzed for this result outcome based on the score on the scale.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pain Rating Loperamide Study Arm | 24 Hour Sensitivity in Lanced Finger to Touch and Pressure | Proportion of participants with no sensitivity | 14 Participants |
| Pain Rating Loperamide Study Arm | 24 Hour Sensitivity in Lanced Finger to Touch and Pressure | Proportion with no sensitivity to pressure | 15 Participants |
| Pain Rating Placebo Study Arm | 24 Hour Sensitivity in Lanced Finger to Touch and Pressure | Proportion of participants with no sensitivity | 6 Participants |
| Pain Rating Placebo Study Arm | 24 Hour Sensitivity in Lanced Finger to Touch and Pressure | Proportion with no sensitivity to pressure | 5 Participants |
Secondary
Change in Beats Per Minute (BPM) Within Groups During Lance One and Lance Two Procedure
BPM obtained using the Kenek Edge Pulse Oximeter System using a flipclop sensor and companion app. Mean BPM during lance initiation through recovery (30 seconds following lance) reported.
Time frame: Average of BPM during each phase of the lance procedure (lance, specimen collection, recovery)
Population: Repeat measures lance one and lance two -
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pain Rating Loperamide Study Arm | Change in Beats Per Minute (BPM) Within Groups During Lance One and Lance Two Procedure | Lance One BPM Average | 74.6 beats per minute (Mean) | Standard Deviation 12 |
| Pain Rating Loperamide Study Arm | Change in Beats Per Minute (BPM) Within Groups During Lance One and Lance Two Procedure | Lance 2 BPM Average | 74.3 beats per minute (Mean) | Standard Deviation 11.4 |
| Pain Rating Placebo Study Arm | Change in Beats Per Minute (BPM) Within Groups During Lance One and Lance Two Procedure | Lance One BPM Average | 74.1 beats per minute (Mean) | Standard Deviation 9.4 |
| Pain Rating Placebo Study Arm | Change in Beats Per Minute (BPM) Within Groups During Lance One and Lance Two Procedure | Lance 2 BPM Average | 71.8 beats per minute (Mean) | Standard Deviation 7.19 |
Comparison: The population BPM lance one = population BPM mean lance two. Loperamide 1= Loperamide 2. Placebo 1=Placebo 2.p-value: 0.876t-test, 1 sided
Comparison: Mean HR during the procedure for lance one will equal mean HR lance two following loperamide gel applciationp-value: 0.085ANOVA
Secondary
Safety- Number of Participants With Treatment Related Adverse Events as Assessed by the CTCAE V.4
CTCAE will be utilized for reporting any adverse events with specific focus on skin and tissue disorders. A Standard erythema scale (0=no effect, 0.5=observer indecisive, 1=faint pink-no border, 1.5=faint pink border, 2=faint pink with one border, 2.5=fain pink with two borders, 3=red, 3.5=fiery red 4=violaceous red will also be used to classify skin erythema.
Time frame: Direct observation of treatment site at one minute and 30 minutes. Participant report at 24 hours if any redness is present on the forearm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pain Rating Loperamide Study Arm | Safety- Number of Participants With Treatment Related Adverse Events as Assessed by the CTCAE V.4 | 0 participants |
| Pain Rating Placebo Study Arm | Safety- Number of Participants With Treatment Related Adverse Events as Assessed by the CTCAE V.4 | 0 participants |
Secondary
Safety - Number of Participants With Treatment Related Adverse Gastrointestinal Disorders Using the CTCAE V. 4 With Focus on Abdominal Pain, Constipation and Diarrhea
Participant report of any abdominal pain or change in stool pattern (constipation or diarrhea) over the past 24 hours using the CTCAE V.4 with focus on abdominal pain, constipation and diarrhea..
Time frame: 24 hour participant report
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pain Rating Loperamide Study Arm | Safety - Number of Participants With Treatment Related Adverse Gastrointestinal Disorders Using the CTCAE V. 4 With Focus on Abdominal Pain, Constipation and Diarrhea | 0 participants |
| Pain Rating Placebo Study Arm | Safety - Number of Participants With Treatment Related Adverse Gastrointestinal Disorders Using the CTCAE V. 4 With Focus on Abdominal Pain, Constipation and Diarrhea | 0 participants |