Clinical trial NCT04160520: Pramipexole and Morphine for Renal Colic
Official title: Adjuvant Treatment With Pramipexole to Reduce the Dose of Opioids Necessary for Analgesia in Acute Renal Colic
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Renal Colic
Keywords: morphine
Pramipexole
Renal Colic
Kidney Stone
opioids
analgesia
pain relief
Lead sponsor: East Carolina University
Sponsor class: OTHER
First posted: 2019-11-13
Enrollment: 19
Sex: ALL
Minimum age (years): 19
Maximum age (years): 66
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Opioid analgesics are among the most commonly prescribed class of medications in the US. While opioids may effectively control pain and other sensory disorders under acute conditions, the rates of misuse/abuse and accidental overdose have reached epidemic proportions. Clinicians are being challenged to find alternatives to opioid analgesics, or to reduce their use in treating pain whenever possible. Pre-clinical studies have shown that combining morphine (opioid drug) with pramipexole (dopamine 3 receptor agonist with some D2/D4 action) provides superior analgesia against painful stimuli than morphine alone. This analgesia is maintained even when the dose of morphine is lowered to a dose that is not effective on its own. A recent case report describes the use of this combination to restore pain control in a patient with restless legs syndrome, for which opioids alone have lost their effectiveness (Happe S, Clemens S and Brewer KL, In Review). This application proposes to establish a new therapeutic approach for treatment of a pain associated with renal colic (a common painful condition) using a novel combination of 2 existing, FDA-approved drugs. The immediate goal is to demonstrate that this drug combination can provide similar analgesia to opioid alone, and that analgesia is maintained when the opioid dose is reduced by 50%.

Detailed description: This is a double-blinded randomized controlled trial to take place in the Vidant Medical Center (VMC) Emergency Department (ED). A convenience sample of 96 participants will be drawn from patients presenting to the ED presentation with pain associated with suspected renal colic who do not experience pain relief after initial treatment with nonsteroidal anti-inflammatories.

Written informed consent will be sought by a study team member after screening to ensure all inclusion criteria and no exclusion criteria are met. Once a patient has consented, they will be randomized into 1 of 2 study arms: Arm 1 (Control arm) = 0.1mg/kg of intravenous morphine + placebo pill, single dose Arm 2 (Study arm) = 0.05mg/kg intravenous morphine + 0.25mg pramipexole, single dose. Both arms include a maximum dose of 10mg/kg for the IV morphine. Pain scores will be obtained prior to administration of study drugs, and at 15-minute intervals (+/- 2 mins) after treatment for up to 2 hours, or discharge from the ED. Subjective response to each drug treatment will also be assessed every 15 minutes (+/- 2 mins) after treatment for up to 2 hours, or discharge from ED. Morphine will have a max dose of 10mg IV.

Eligibility criteria: Inclusion Criteria:

* Age 19 - 65
* ED presentation with pain associated with suspected renal colic
* Patient reported failure to achieve pain relief with NSAID treatment in ED (additional pain treatment needed per treatment team)

Exclusion Criteria:

* Age \< 19 or ≥ 66
* Allergy to any study medication
* Known pregnancy or breastfeeding
* Received opioid prior to enrollment
* Received IV Lidocaine during current ED visit
* Known chronic renal disease
* Currently taking any dopamine receptor agonist or antagonists (Do I need to list?)
* Unable to consent

Primary outcomes:
measure: Proportion of patients who have an effective analgesic response (defined as at least a 50% improvement in pain scores) at 120 minutes post-randomization.
timeFrame: 120 minutes
measure: Total dose of opioid received at 120 minutes in patients reporting a reduction in pain scores from baseline.
timeFrame: 120 minutes
measure: Proportion of patients who require rescue medications at 30 minutes post-randomization.
timeFrame: 30 minutes
Secondary outcomes:
measure: Time to reach effective pain reduction (defined as at least a 50% improvement in pain scores) within 120 minutes of treatment.
timeFrame: 120 minutes
measure: Subjective effects of the drugs measured by scores on the drug effects questionnaire.
timeFrame: 120 minutes
Other outcomes:
Locations:
city: Greenville
country: United States
facility: Vidant Medical Center ED
state: North Carolina
Study officials:
affiliation: East Carolina University
name: Kori Brewer, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rodgers HM, Yow J, Evans E, Clemens S, Brewer KL. Dopamine D1 and D3 receptor modulators restore morphine analgesia and prevent opioid preference in a model of neuropathic pain. Neuroscience. 2019 May 15;406:376-388. doi: 10.1016/j.neuroscience.2019.03.034. Epub 2019 Mar 23.
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