Pramipexole and Morphine for Renal Colic
Condition: Renal Colic
MeSH terms: Colic; Renal Colic
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

Intervention name(s): Pramipexole; Morphine; Placebo oral tablet
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Establish proof of concept that low dose morphine in combination with pramipexole is non-inferior to standard dose morphine with respect to providing analgesia in patients presenting to the ED with pain associated with renal colic.; Establish proof of concept that low dose morphine in combination with pramipexole is non-inferior to standard dose morphine with respect to providing analgesia in patients presenting to the ED with pain associated with renal colic.; Establish proof of concept that low dose morphine in combination with pramipexole is non-inferior to standard dose morphine with respect to providing analgesia in patients presenting to the ED with pain associated with renal colic.
Intervention MeSH terms: Morphine; Pramipexole
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: morphine; Pramipexole; Renal Colic; Kidney Stone; opioids; analgesia; pain relief