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| ID | Type | Description | Link |
|---|---|---|---|
| IND 122919 | Other Identifier | Food and Drug Administration |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 5% Loperamide gel | Experimental | 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%. |
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| Placebo gel | Placebo Comparator | 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%. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Loperamide | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Within one minute following each lance |
| 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. | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 24 hours following the second lance. |
| 24 Hour Sensitivity in Lanced Finger to Touch and Pressure |
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Inclusion Criteria:
Exclusion Criteria:
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 6493791 | Background | Owens ME, Todt EH. Pain in infancy: neonatal reaction to a heel lance. Pain. 1984 Sep;20(1):77-86. doi: 10.1016/0304-3959(84)90813-3. | |
| 10857956 | Background | 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. doi: 10.2337/diacare.23.4.562. No abstract available. |
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| ID | Type | URL | Comment |
|---|---|---|---|
| Loperamide | Study Protocol | View IPD |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 5% Loperamide Gel | 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 and then 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 forearm was also swabbed with the loperamide gel which was left in place for 30 minutes. The loperamide gel formulation includes: Loperamide 5%, Propylene Glycol; Ethanol (190 proof USP); Ethyl acetate; and Klucel HF 1%. |
| FG001 | Placebo Gel | 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%. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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All participants completed the study.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | The age range was 18-72 years and there was no difference in mean age between the loperamide group (M 42years) and the placebo group (M 39 years). |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Mean | Standard Deviation | units on a scale | Within one minute following each lance |
|
Adverse events were collected at 24 hours.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kathleen C. Heneghan, RN, PhD | Rush University Medical Center | 3123395943 | kheneghan@facs.org |
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| ID | Term |
|---|---|
| D010146 | Pain |
| ID | Term |
|---|---|
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D008139 | Loperamide |
| D004364 | Pharmaceutical Preparations |
| ID | Term |
|---|---|
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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|
| Drug, placebo gel | Drug | 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. |
|
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. |
| 24 hours post lancing. |
| 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. | Average of BPM during each phase of the lance procedure (lance, specimen collection, recovery) |
| 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 using the CTCAE V.4 with focus on abdominal pain, constipation and diarrhea.. | 24 hour participant report |
| 3960577 | Background | Johnston CC, Strada ME. Acute pain response in infants: a multidimensional description. Pain. 1986 Mar;24(3):373-382. doi: 10.1016/0304-3959(86)90123-5. |
| 7760870 | Background | Stein C. The control of pain in peripheral tissue by opioids. N Engl J Med. 1995 Jun 22;332(25):1685-90. doi: 10.1056/NEJM199506223322506. No abstract available. |
| 12894165 | Background | Stein C, Schafer M, Machelska H. Attacking pain at its source: new perspectives on opioids. Nat Med. 2003 Aug;9(8):1003-8. doi: 10.1038/nm908. |
| 10087042 | Background | 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. |
| 9915332 | Background | 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. doi: 10.1097/00000542-199901000-00029. |
| 17273395 | Background | Page GG. Are there long-term consequences of pain in newborn or very young infants? J Perinat Educ. 2004 Summer;13(3):10-7. doi: 10.1624/105812404X1725. |
| Background | Osborne DW. (2002). Patent No. US 6355657 B1. US. https://www.google.com/patents/US6355657 Accessed June 1, 2014 |
Contact the Rush Office of Research Affairs for all materials 312 942-5498 |
| Loperamide | Informed Consent Form | View IPD | Contact the Rush Office of Research Affairs for all materials 312 942-5498 |
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| Mean |
| Full Range |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Anxiety to needle stick scale | The anxiety about needle sticks scale range is 0-10 with 0 (0=not at all anxious) to 10 (worst imaginable). Prior to the first finger lance, participants were asked "How anxious (nervous) do you get about having a stick for blood drawing?" and circled their response on a print form as part of their demographic data. | Mean | Standard Deviation | units on a scale |
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| OG001 | Pain Rating Placebo Study Arm | The 5th digit finger pad of the non-dominant hand was cleaned with 70% alcohol. The participant was asked to look away and the finger pad was punctured using a single-use lancet which contains a stainless steel blade automatic trigger and retractor that incises with a 21 guage needle to a controlled depth of 2.2 mm and with of 0.8 mm. The pain rating was obtained within one minute following the lance. Ten minutes following lance one, 0.2 grams of Placebo gel was applied using a circular mold to the lance site and left in place for 30 minutes. At 30 minutes, the gel was removed, site cleansed with alcohol and lanced in the same location. The second pain rating was obtained within one minute of the lance. |
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| 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. | Posted | Count of Participants | Participants | 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. |
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| 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 | Posted | Mean | Standard Deviation | score on a scale | 24 hours following the second lance. |
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| 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. | 17 participants from both groups/arms were analyzed for this result outcome based on the score on the scale. | Posted | Count of Participants | Participants | 24 hours post lancing. |
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| 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. | Repeat measures lance one and lance two - | Posted | Mean | Standard Deviation | beats per minute (Mean) | Average of BPM during each phase of the lance procedure (lance, specimen collection, recovery) |
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| 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. | Posted | Number | participants | Direct observation of treatment site at one minute and 30 minutes. Participant report at 24 hours if any redness is present on the forearm. |
|
|
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| 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.. | Posted | Number | participants | 24 hour participant report |
|
|
|
| 0 |
| 17 |
| 0 |
| 17 |
| EG001 | 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. | 0 | 17 | 0 | 17 |
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| Participants rating pain a little more |
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| Participants rating pain much more |
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| Participants rating pain about the same |
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| 2-Sided |
| .05 |
| Superiority or Other (legacy) |
Mean HR during the procedure for lance one will equal mean HR lance two following loperamide gel applciation
| ANOVA |
df 16. |
| .085 |
Comparison of the mean between HR one and HR two during the procedure for lance one will equal the mean HR lance two following loperamide gel application. |
| Superiority or Other (legacy) |