Topical Loperamide Gel for Pain Reduction During Repeat Finger Lancing

Pain Clinical Trial

— Loperamide  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02711891
• Other study ID #: 13091401-IRB02
• Secondary ID: IND 122919
• Status: Completed
• Phase: Early Phase 1
• First received: December 11, 2015
• Last updated: March 16, 2016
• Start date: March 2015
• Est. completion date: December 2015

Study information

• Verified date: March 2016
• Source: Rush University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Pain

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Rush University Medical Center

References & Publications (9)

DeHaven-Hudkins DL, Burgos LC, Cassel JA, Daubert JD, DeHaven RN, Mansson E, Nagasaka H, Yu G, Yaksh T. Loperamide (ADL 2-1294), an opioid antihyperalgesic agent with peripheral selectivity. J Pharmacol Exp Ther. 1999 Apr;289(1):494-502. — View Citation

Fruhstorfer H, Schmelzeisen-Redeker G, Weiss T. Capillary blood volume and pain intensity depend on lancet penetration. Diabetes Care. 2000 Apr;23(4):562-3. — View Citation

Johnston CC, Strada ME. Acute pain response in infants: a multidimensional description. Pain. 1986 Mar;24(3):373-82. — View Citation

Nozaki-Taguchi N, Yaksh TL. Characterization of the antihyperalgesic action of a novel peripheral mu-opioid receptor agonist--loperamide. Anesthesiology. 1999 Jan;90(1):225-34. — View Citation

Osborne DW. (2002). Patent No. US 6355657 B1. US. https://www.google.com/patents/US6355657 Accessed June 1, 2014

Owens ME, Todt EH. Pain in infancy: neonatal reaction to a heel lance. Pain. 1984 Sep;20(1):77-86. — View Citation

Page GG. Are there long-term consequences of pain in newborn or very young infants? J Perinat Educ. 2004 Summer;13(3):10-7. — View Citation

Stein C, Schäfer M, Machelska H. Attacking pain at its source: new perspectives on opioids. Nat Med. 2003 Aug;9(8):1003-8. Review. — View Citation

Stein C. The control of pain in peripheral tissue by opioids. N Engl J Med. 1995 Jun 22;332(25):1685-90. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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.
Secondary	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
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.	Direct observation of treatment site at one minute and 30 minutes. Participant report at 24 hours if any redness is present on the forearm.
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.	24 hour participant report