Pain
Conditions
Brief summary
This research study is being done to assess if a combination of medications can enhance the relief of superficial pain (pain at the surface of the skin, such as sunburn pain). The investigators also want to find out if certain genes may be linked to individual differences in experienced efficacy of pain killers. The combination of medications under investigation is diclofenac and atropine. Diclofenac has been approved by the U.S. Food and Drug Administration (FDA) to treat pain. Atropine has been approved by the FDA to treat certain types of poisoning, heartbeat problems, and other diseases but atropine is not approved to treat pain. However, atropine has been used for many years in different European countries to treat painful conditions such as stomach cramps.This research study will compare diclofenac and atropine to placebo.
Interventions
DRUGDiclofenac and Atropine combination drug
Diclofenac will be associated with a small dose of atropine 1.2mg
DRUGPlacebo
For each capsule of active medication, a capsule of placebo will be provided, identical looking.
Sponsors
Beth Israel Deaconess Medical Center
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Male and female healthy volunteers. * 18-40 years of age. * Ability to read and understand English; English can be a second language provided that the participant feels that he/she understand all the questions used in the assessment measures.
Exclusion criteria
* Chronic pain condition or chronic or current treatment with any pain medication. * Presence of any illness or medication use that is judged to interfere with the trial. For example: psychiatric disorder, medication that can influence cognition or emotional processing, i.e. sleep medication, antidepressants, anti-convulsants or opioids. * Unwillingness to receive brief pain stimulation administered by a heat probe on the hand. * Allergy or contra-indication to receiving nonsteroidal anti-inflammatory medication and atropine (Treatment with antidepressants, neuroleptics, antihistaminic, levodopa, anti-acids. Pregnancy, breast-feeding, myasthenia gravis, pyloric stenosis, gastro-esophageal reflux, gastric ulcer, constipation, prostatic enlargement, glaucoma, cardio-pulmonary condition -including tachycardia, arrhythmia, arteriosclerosis-, hyperthyroidism, high blood pressure, genetic disease, kidney failure)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain Scores on Standardized Experimental Pain Testing | baseline and 1 hour pain measurement | Pain scores on standardized experimental pain testing, with collection of Visual analog scales (VAS) on a 0-100 scale 0 (no pain)- 100 (worst pain imaginable) Higher values represent a worse outcome (more pain) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Catechol-O-methyltransferase (COMT) Polymorphism Correlation With Pain Relief | baseline and 1 hour pain measurement | Difference in the baseline pain measurements compared to the 1-hour outcome measure will be correlated with Catechol-O-methyltransferase polymorphism |
| Side Effects | baseline and 1 hour pain measurement | The investigators aimed assess if these would be a reason for discontinuation of treatment in a population with mild to moderate pain.Side effects will be assessed with a dichotomous measurement (yes/no) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pain Medication: Diclofenac and Atropine Diclofenac and Atropine combination drug Provided PO. This is a novel combination. Diclofenac 100mg + Atropine 1.2 mg in one single dose
Diclofenac and Atropine combination drug: Diclofenac will be associated with a small dose of atropine 1.2mg | 75 |
| Placebo Placebo capsules will be delivered in same number as the medication
Placebo: For each capsule of active medication, a capsule of placebo will be provided, identical looking. | 25 |
| Total | 100 |
Baseline characteristics
| Characteristic | Placebo | Pain Medication: Diclofenac and Atropine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants | 75 Participants | 100 Participants |
| Age, Continuous | 23.16 years STANDARD_DEVIATION 3.94 | 24.04 years STANDARD_DEVIATION 4.75 | 23.82 years STANDARD_DEVIATION 4.56 |
| Region of Enrollment United States | 25 participants | 75 participants | 100 participants |
| Sex: Female, Male Female | 14 Participants | 37 Participants | 51 Participants |
| Sex: Female, Male Male | 11 Participants | 38 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 75 | 0 / 25 |
| other Total, other adverse events | 0 / 75 | 0 / 25 |
| serious Total, serious adverse events | 0 / 75 | 0 / 25 |
Outcome results
Primary
Pain Scores on Standardized Experimental Pain Testing
Pain scores on standardized experimental pain testing, with collection of Visual analog scales (VAS) on a 0-100 scale 0 (no pain)- 100 (worst pain imaginable) Higher values represent a worse outcome (more pain)
Time frame: baseline and 1 hour pain measurement
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pain Medication: Diclofenac and Atropine | Pain Scores on Standardized Experimental Pain Testing | Baseline | 59.6 units on a scale | Standard Deviation 13.9 |
| Pain Medication: Diclofenac and Atropine | Pain Scores on Standardized Experimental Pain Testing | 1 hour Assessment | 44.1 units on a scale | Standard Deviation 22.7 |
| Placebo | Pain Scores on Standardized Experimental Pain Testing | Baseline | 54.0 units on a scale | Standard Deviation 13.9 |
| Placebo | Pain Scores on Standardized Experimental Pain Testing | 1 hour Assessment | 45.3 units on a scale | Standard Deviation 18 |
Secondary
Catechol-O-methyltransferase (COMT) Polymorphism Correlation With Pain Relief
Difference in the baseline pain measurements compared to the 1-hour outcome measure will be correlated with Catechol-O-methyltransferase polymorphism
Time frame: baseline and 1 hour pain measurement
Population: Data were not collected
Secondary
Side Effects
The investigators aimed assess if these would be a reason for discontinuation of treatment in a population with mild to moderate pain.Side effects will be assessed with a dichotomous measurement (yes/no)
Time frame: baseline and 1 hour pain measurement
Population: Participants were analyzed in terms of whether they endorsed or not the side effects (yes/no) Participants were not analyzed in terms of severity degree
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pain Medication: Diclofenac and Atropine | Side Effects | Other Side Effects | 4 Participants |
| Pain Medication: Diclofenac and Atropine | Side Effects | Dry mouth | 28 Participants |
| Pain Medication: Diclofenac and Atropine | Side Effects | No side effects | 43 Participants |
| Placebo | Side Effects | Dry mouth | 7 Participants |
| Placebo | Side Effects | Other Side Effects | 2 Participants |
| Placebo | Side Effects | No side effects | 16 Participants |