Efficacy Study Comparing Compounded Topical Pain Creams vs. Placebo for Treating Pain Symptoms

Randomized, Controlled, Double-blind, Efficacy Study Comparing Compounded Topical Pain Creams vs. Placebo for Treating Pain Symptoms

The main objective of this protocol is to determine the effectiveness of using compounded topical pain creams for treating neuropathic, nociceptive, or mixed-pain syndromes. Since these compounded pain creams may be associated with burning or irritation at the application site, and possible systemic effects may present, the secondary objective is to determine the relative satisfaction with the creams. The investigators hypothesis is that the active pain creams may provide significant benefit compared to placebo cream.

3.1 Specific Aims

1. Specific Aim 1 will determine pain relief following treatment with the appropriate (based on specified pain) compounded topical pain cream or a placebo cream. The investigators hypothesis is that the compounded topical pain creams will provide greater pain relief than placebo creams.
2. Specific Aim 2 will measure the patient satisfaction with the cream (compound or placebo). The investigators hypothesis is that the compounded topical pain creams will improve patient satisfaction, while the placebo cream will not result in a change in patient satisfaction with their pain treatment.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Other: Neuropathic pain cream; Other: Nociceptive pain cream; Other: Mixed pain cream

Detailed Description

In this study, the investigators are attempting to determine whether compounded topical pain creams are more effective than placebo; as well as measuring the subjects' satisfaction with the compounded pain creams. Three different compounded pain creams (specific to the type of pain being treated) will be used to examine effectiveness and satisfaction in treating neuropathic, nociceptive, or mixed pain syndromes. Up to 399 subjects will be randomized to receive a compounded pain cream or placebo. The type of pain cream to be used will be based on the subjects' pain diagnosis. Pain relief will be measured by a 0-10 Numeric Rating Scale and satisfaction by a 1-5 Likert Satisfaction Scale. The outcome measures will include a 'positive outcome' defined as a two point or greater reduction in average pain (as measured by a NRS) and a score of greater than 3 (on a 1-5 Likert scale measuring satisfaction) at 1-month. The investigators will use the Rand Corporation SF-36 to measure changes in health status during enrollment. Subjects who obtain benefit at 1-month will be followed at 3-months, while those who fail to obtain benefit (i.e., ≥ 2 point reduction in NRS with a greater than 3 Likert satisfaction score) will exit the study to receive alternative care. Patients will be given a pain diary so that their NRS can be calculated at follow up visits.

• Study Type: Interventional
• Enrollment (Actual): 399
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age > 18;-90
2. A localized pain complaint to include: the back, neck, face, groin, buttocks, abdomen, chest, or up to two extremities
3. Average pain score ≥ 4/10 over the past week;
4. Pain duration > 6 weeks
5. DEERS eligibility.

Exclusion Criteria:

1. Previous prescription for a compounded pain cream.
2. Cannot read or understand English.
3. Allergic reaction to Ketamine, Gabapentin, Diclofenac, Baclofen, Cyclobenzaprine, Ketoprofen, Clonidine or lidocaine.
4. Pregnancy. Ruling out pregnancy will be done in accordance with our standard procedures, which is to obtain a urine HCG in any female of child-bearing age who may be pregnant prior to starting any new medications.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Neuropathic Pain; Subjects with neuropathic pain will receive a neuropathic pain cream combined of Ketamine 10%/Gabapentin 6%/Clonidine 0.2% and Lidocaine 2% or placebo. They will be told to use the pain cream 3 times per day. Each will receive cream in identical dispensers. Cream is dispensed by rotating the base of the device and each rotation also produces a clicking sound. The number of clicks will be standardized so that all doctors utilize the same prescription depending on the size of the patient's pain location.	Other: Neuropathic pain cream; Subjects will apply the cream to the painful area.
Placebo Comparator: Nociceptive pain; Subjects with nociceptive pain will receive a nociceptive pain cream combined of Ketoprofen 10%/Baclofen 2%/Cyclobenzaprine 2% and Lidocaine 2% or placebo. They will be told to use the pain cream 3 times per day. Each will receive cream in identical dispensers. Cream is dispensed by rotating the base of the device and each rotation also produces a clicking sound. The number of clicks will be standardized so that all doctors utilize the same prescription depending on the size of the patient's pain location.	Other: Nociceptive pain cream; Subjects will apply the cream to the painful area.
Placebo Comparator: Mixed pain; Subjects who have a mixed (nociceptive and neuropathic) pain conditions will receive a mixed pain cream combined of Ketamine 10%/Gabapentin 6%/Diclofenac 3%/baclofen 2%/Cyclobenzaprine 2% and Lidocaine 2% or placebo. They will be told to use the pain cream 3 times per day. Each will receive cream in identical dispensers. Cream is dispensed by rotating the base of the device and each rotation also produces a clicking sound. The number of clicks will be standardized so that all doctors utilize the same prescription depending on the size of the patient's pain location.	Other: Mixed pain cream; Subjects will apply the cream to the painful area.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Numerical Pain Rating Scale (NPRS) 0-10	The Numerical Pain Rating Scale is a unidimensional measure of pain intensity. It is an 11 point numerical scale (with 0 meaning no pain; and 10 meaning the worst possible pain imaginable) used to assess pain intensity for persons able to self-report.	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Health Status via Rand Corporation SF-36	The SF-36 is a 36 item Short Form Health Survey that is used to measure changes in health status. It is a set of generic, coherent, and easily administered quality-of-life measures. It is a validated measure of 8 domains including emotional health and physical function, with lower scores translating to greater disability.	1 month
5-point Likert Satisfaction Scale (1-5)	The 5-point Likert Satisfaction Scale is a 5 point scale that is used to measure the subjects opinion/perception of their satisfaction with the compounded product. The scale ranges from 1-5; with 1 denoting "very unsatisfied" and 5 signifying "very satisfied."	1 month
Composite outcome determined by combining the subjects average change in pain score measured by the Numerical Pain Rating Scale and their score on the 5-point Likert Satisfaction Scale.	A positive composite outcome was defined as a decrease in average pain of 2 points or greater and a satisfaction score greater than 3.	1 month
Numerical Pain Rating Scale (NPRS) 0-10	The Numerical Pain Rating Scale is a unidimensional measure of pain intensity. It is an 11 point numerical scale (with 0 meaning no pain; and 10 meaning the worst possible pain imaginable) used to assess pain intensity for persons able to self-report.	3 months
Change in Health Status via Rand Corporation SF-36	The SF-36 is a 36 item Short Form Health Survey that is used to measure changes in health status. It is a set of generic, coherent, and easily administered quality-of-life measures. It is a validated measure of 8 domains including emotional health and physical function, with lower scores translating to greater disability.	3 Months
5-point Likert Satisfaction Scale (1-5)	The 5-point Likert Satisfaction Scale is a 5 point scale that is used to measure the subjects opinion/perception of their satisfaction with the compounded product. The scale ranges from 1-5; with 1 denoting "very unsatisfied" and 5 signifying "very satisfied."	3 months

Collaborators and Investigators

• Sponsor: Walter Reed National Military Medical Center
• Investigators: Principal Investigator: Robert E Brutcher, PharmD,Ph.D., WRNMMC

Publications and helpful links

General Publications

• Brutcher RE, Kurihara C, Bicket MC, Moussavian-Yousefi P, Reece DE, Solomon LM, Griffith SR, Jamison DE, Cohen SP. Compounded Topical Pain Creams to Treat Localized Chronic Pain: A Randomized Controlled Trial. Ann Intern Med. 2019 Mar 5;170(5):309-318. doi: 10.7326/M18-2736. Epub 2019 Feb 5.

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2015
• Primary Completion (Actual): February 28, 2018
• Study Completion (Actual): February 28, 2018

Study Registration Dates

• First Submitted: June 30, 2015
• First Submitted That Met QC Criteria: July 10, 2015
• First Posted (Estimate): July 14, 2015

Study Record Updates

• Last Update Posted (Actual): May 28, 2019
• Last Update Submitted That Met QC Criteria: May 23, 2019
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: pain; topical; compound
• Additional Relevant MeSH Terms: Neurologic Manifestations; Pain
• Other Study ID Numbers: #412770-2