Topical Loperamide Gel for Pain Reduction During Repeat Finger Lancing

Study Overview
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Brief Summary
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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
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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.

Official Title
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Topical Loperamide Gel for Pain Reduction During Repeat Finger Lancing: A Randomized Double Blind Trial

Conditions
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Pain

Intervention / Treatment
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* Drug: Loperamide
* Drug: Drug, placebo gel


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 5% Loperamide gel<br>Participants received 5% loperamide gel (0.2gm equivalent to 10 mg) applied following a single surgilance to the 5th digit. The loperamide gel was applied 10 minutes following the first lance, rubbed in for one minute within an 8 mm mold surrounding the lance site. The mold was removed and the gel was covered with a transparent occlusive dressing and left in place for 30 minutes. The forearm was also swabbed with the loperamide gel which was left in place for 30 minutes. The placebo gel contained the same ingredients without the loperamide. The loperamide gel formulation includes: Loperamide 5%, Propylene Glycol; Ethanol (190 proof USP); Ethyl acetate; and Klucel HF 1%. | Drug: Loperamide<br>* 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.<br>* Other names: Mu opioid receptor agonist;|
| Placebo Comparator: Placebo gel<br>Participants received placebo gel (0.2gm) applied following a single surgilance to the 5th digit. The placebo gel was applied 10 minutes following the first lance, rubbed in for one minute within an 8 mm mold surrounding the lance site. The mold was removed and the gel was covered with a transparent occlusive dressing and left in place for 30 minutes. The forearm was also swabbed with the placebo gel which was left in place for 30 minutes. .The placebo gel contained the same ingredients without the loperamide. The placebo gel formulation includes: Propylene Glycol; Ethanol (190 proof USP); Ethyl acetate; and Klucel HF 1%. | Drug: Drug, placebo gel<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain - Numeric Rating Scale | Subject reported mean pain score following a finger lance on a rating scale of 0 (no pain) to 10 (worst pain). | Within one minute following each lance | 
| Pain - comparative pain scale | Comparative rating scale includes: much less, a little less, about the same, a little more or much more. | 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. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reported numeric pain rating and sensitivity to touch and pressure in the lanced finger site. | Number of participants reporting pain or sensitivity in the lanced finger site obtained via text using the numeric rating scale 0-10 )=no pain and 10 = worst pain ever. Sensitivity questions adapted from the pain quality assessment scale, please tell us how sensitive your fingerstick site has been to light touch or clothing rubbing against it over the past day (0=non-sensitive; 1-sensitive); Please tell us how tender your fingerstick site is when something has pressed against it in the past day (0=not tender and 1=tender) | 24 hours following the second lance. | 
| Change in heart rate from baseline during the lance procedure | heart rate measured and recorded using Kenek Edge oxygen saturation and heart rate monitor attached to middle finger on dominant hand | Heart rate 10 second interval average during the one minute lance procedure starting 30 seconds pre-lance, skin lance and 30 seconds post lance | 
| 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. | Direct observation of treatment site at one minute and 30 minutes. Participant report at 24 hours if any redness is present on the forearm. | 
| 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. | 24 hour participant report | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fingerstick, opioid, heelstick, loperamide, topical opioid