Pramipexole and Morphine for Renal Colic

University of North Carolina System

Status and phase: Completed; Phase 2; Phase 1

Conditions: Renal Colic

Treatments: Drug: Placebo oral tablet; Drug: Pramipexole; Drug: Morphine

Study type: Interventional

Funder types: Other

Identifiers

NCT04160520

ECarolinaUniversity

Details and patient eligibility

About

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%.

Full 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.

Enrollment: 19 patients

Sex: All

Ages: 19 to 66 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

19 participants in 2 patient groups

Pramipexole and half-standard dose of morphine

Experimental group

Description:

0.25 mg oral tablet of pramipexole in combination with 0.05mg/kg of IV morphine

Treatment:

Drug: Morphine

Drug: Pramipexole

Standard dose of morphine and placebo

Active Comparator group

Description:

0.1mg/kg of IV morphine in combination with a placebo pill

Treatment:

Drug: Morphine

Drug: Placebo oral tablet