Pramipexole and Morphine for Renal Colic

Sponsor

East Carolina University (Other)

Overall Status

Unknown status

CT.gov ID

NCT04160520

Collaborator

(none)

Enrollment

Location

Arms

13.1

Anticipated Duration (Months)

7.3

Patients Per Site Per Month

Study Details

Study Description

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%.

Condition or Disease	Intervention/Treatment	Phase
Renal Colic	Drug: Pramipexole Drug: Morphine Drug: Placebo oral tablet	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

96 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Masking Description:

Participant and study team (i.e. investigators responsible for collecting pain scores) will be blinded as to treatment arm for the duration of the study (2 hours after initiation or until ED discharge/hospital admission). Treatment team (physicians and nurses involved in ED care of the patient) will be unblinded to maintain participant safety and proper medication administration. While the treating physician may be aware of what drugs have been ordered, the need for rescue medications is based on patient pain score at the 30-minute point.

Primary Purpose:

Treatment

Official Title:

Adjuvant Treatment With Pramipexole to Reduce the Dose of Opioids Necessary for Analgesia in Acute Renal Colic

Actual Study Start Date :

Oct 28, 2019

Anticipated Primary Completion Date :

Nov 1, 2020

Anticipated Study Completion Date :

Dec 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pramipexole and half-standard dose of morphine 0.25 mg oral tablet of pramipexole in combination with 0.05mg/kg of IV morphine	Drug: Pramipexole 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. Drug: Morphine 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.
Active Comparator: Standard dose of morphine and placebo 0.1mg/kg of IV morphine in combination with a placebo pill	Drug: Morphine 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. Drug: Placebo oral tablet 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.

Arm

Intervention/Treatment

Experimental: Pramipexole and half-standard dose of morphine

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

Drug: Pramipexole

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.

Drug: Morphine

Active Comparator: Standard dose of morphine and placebo

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

Drug: Morphine

Drug: Placebo oral tablet

Outcome Measures

Primary Outcome Measures

Proportion of patients who have an effective analgesic response (defined as at least a 50% improvement in pain scores) at 120 minutes post-randomization. [120 minutes]
Pain scores used are the numerical rating scale (0 low to 10 high) or visual analogue scale (0 low to 100mm high).
Total dose of opioid received at 120 minutes in patients reporting a reduction in pain scores from baseline. [120 minutes]
Dose of opioid measured in mg/kg
Proportion of patients who require rescue medications at 30 minutes post-randomization. [30 minutes]

Secondary Outcome Measures

Time to reach effective pain reduction (defined as at least a 50% improvement in pain scores) within 120 minutes of treatment. [120 minutes]
Pain scores used are the numerical rating scale (0 low to 10 high) or visual analogue scale (0 low to 100mm high).
Subjective effects of the drugs measured by scores on the drug effects questionnaire. [120 minutes]
Drug effects questionnaire rates symptoms from 'not at all' at 0mm to 'extremely' at 100mm.

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years to 66 Years

Sexes Eligible for Study:

All

Accepts 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