Pain
Conditions
Keywords
pain, chronic pain, clonidine, adenosine, complex regional pain syndrome, CRPS, a2-adrenergic agonists, alpha2-adrenergic agonists
Brief summary
The purpose of this study is to determine the effects of clonidine and adenosine on nerve pain.
Detailed description
This study is part of a pain center grant that focuses on how pain, especially chronic neuropathic pain, alters the response to traditional and non-traditional analgesics (pain medications). Clonidine-a drug commonly used to treat high blood pressure-has been shown to effectively treat neuropathic pain, is FDA-approved for administration via epidural (an injection given in the lower back), and is the third most commonly prescribed drug for chronic intrathecal (an injection into the cerebrospinal fluid) use in people with chronic pain. Adenosine-a drug commonly administered intravenously (into a vein) to treat certain types of abnormal heart rhythms-has been found to reduce areas of allodynia (pain caused by a stimulus that does not normally cause pain) after intrathecal, but not intravenous administration in people with neuropathic pain. Intrathecal clonidine relieves pain by actions on a2-adrenoceptors in the spinal cord, whereas adenosine relieves pain by actions on A1 adenosine receptors. Researchers believe that intrathecal adenosine and clonidine may prove to be excellent painkillers for nerve pain. Therefore, the goal of this study is to determine the effects of clonidine and adenosine on nerve pain. After initial screening, baseline measurements, and training to learn to estimate pain accurately using thermal heat testing, a sample of spinal fluid will be taken from each participant. Participants then will be randomly chosen to receive either clonidine, adenosine, or placebo. After receiving the study medication, participants will be monitored, with their vital signs checked at 30, 60, 120, 180, and 240 minutes. Duration of the study for participants is 2 weeks, and includes two visits to the research center, each lasting approximately 6 hours.
Interventions
DRUGclonidine
Clonidine-a drug commonly used to treat high blood pressure-has been shown to effectively treat neuropathic pain, is FDA-approved for administration via epidural (an injection given in the lower back), and is the third most commonly prescribed drug for chronic intrathecal (an injection into the cerebrospinal fluid) use in people with chronic pain.
DRUGadenosine
Adenosine-a drug commonly administered intravenously (into a vein) to treat certain types of abnormal heart rhythms-has been found to reduce areas of allodynia (pain caused by a stimulus that does not normally cause pain) after intrathecal, but not intravenous administration in people with neuropathic pain.
DRUGplacebo
inactive substance
Sponsors
National Institute of Neurological Disorders and Stroke (NINDS)
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Patients with complex regional pain syndrome (CRPS), type I involving a lower extremity
Exclusion criteria
* Pregnancy * Allergy to clonidine * Currently taking clonidine or other direct a2-adrenergic agonists, or taking cholinesterase inhibitors * Patients with any serious or unstable medical problems (heart, lung, liver, kidney, or nervous system disease)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number Meeting Success Criterion | baseline and 2 hours | Verbal pain report 2 hours post injection compared to baseline verbal pain scores prior to injection |
Countries
United States
Participant flow
Recruitment details
24 Subjects with chronic pain were recruited from the Center for Clinical Research. Each subject was scheduled for a study visit and randomized to receive spinal clonidine, spinal adenosine or placebo. The subject was scheduled for a second study visit and received the opposite treatment from the first visit.
Pre-assignment details
24 subjects consented and enrolled 2 subjects withdrawn prior to group assignment because they did not meet inclusion / exclusion criteria on second review
Participants by arm
| Arm | Count |
|---|---|
| Clonidine First, Then Adenosine clonidine given in first injection adenosine given in second injection | 10 |
| Adenosine Given First, Then Clonidine adenosine given in first injection clonidine given in second injection | 10 |
| Clonidine Given First, Then Placebo clonidine given first placebo given in second injection | 1 |
| Adenosine First, Then Placebo adenosine given in first injection placebo given in second injection | 1 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| First Spinal Injection | Adverse Event | 0 | 0 | 1 | 0 |
| First Spinal Injection | Physician Decision | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Adenosine Given First, Then Clonidine | Clonidine Given First, Then Placebo | Clonidine First, Then Adenosine | Adenosine First, Then Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 1 Participants | 10 Participants | 1 Participants | 22 Participants |
| Age, Continuous | 43.7 years STANDARD_DEVIATION 10.8 | 19 years STANDARD_DEVIATION 0 | 45.2 years STANDARD_DEVIATION 6.4 | 54 years STANDARD_DEVIATION 0 | 43.7 years STANDARD_DEVIATION 10.1 |
| Region of Enrollment United States | 10 participants | 1 participants | 10 participants | 1 participants | 22 participants |
| Sex: Female, Male Female | 4 Participants | 1 Participants | 8 Participants | 1 Participants | 14 Participants |
| Sex: Female, Male Male | 6 Participants | 0 Participants | 2 Participants | 0 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 11 | 0 / 11 | 0 / 1 | 0 / 1 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 | 0 / 1 | 0 / 1 |
Outcome results
Primary
Number Meeting Success Criterion
Verbal pain report 2 hours post injection compared to baseline verbal pain scores prior to injection
Time frame: baseline and 2 hours
Population: The primary outcome measure will be % change in pain report 2 hr following injection, using a response criterion of 30% reduction in ongoing pain.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clonidine | Number Meeting Success Criterion | 10 participants meeting success criterion |
| Adenosine | Number Meeting Success Criterion | 5 participants meeting success criterion |
| Placebo | Number Meeting Success Criterion | 0 participants meeting success criterion |
Comparison: Null hypothesis is that there is no difference between the groups in proportion of patients meeting the success criterion of \>30% reduction in visual analog scale pain 120 min after intrathecal injectionp-value: >0.05Chi-squared