Pramipexole and Morphine for Renal Colic

Renal Colic Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04160520
• Other study ID #: ECarolinaUniversity
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: October 28, 2019
• Est. completion date: January 24, 2023

Study information

• Verified date: March 2023
• Source: East Carolina University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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%.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: January 24, 2023
• Est. primary completion date: January 24, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 66 Years

Eligibility

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

Related Conditions & MeSH terms

• Colic
• Renal Colic

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	Vidant Medical Center ED	Greenville	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
East Carolina University

Country where clinical trial is conducted

United States, 

References & Publications (12)

Afshar K, Jafari S, Marks AJ, Eftekhari A, MacNeily AE. Nonsteroidal anti-inflammatory drugs (NSAIDs) and non-opioids for acute renal colic. Cochrane Database Syst Rev. 2015 Jun 29;(6):CD006027. doi: 10.1002/14651858.CD006027.pub2. — View Citation

Altun A, Ozdemir E, Yildirim K, Gursoy S, Durmus N, Bagcivan I. The effects of endocannabinoid receptor agonist anandamide and antagonist rimonabant on opioid analgesia and tolerance in rats. Gen Physiol Biophys. 2015 Oct;34(4):433-40. doi: 10.4149/gpb_2015017. — View Citation

Altun A, Yildirim K, Ozdemir E, Bagcivan I, Gursoy S, Durmus N. Attenuation of morphine antinociceptive tolerance by cannabinoid CB1 and CB2 receptor antagonists. J Physiol Sci. 2015 Sep;65(5):407-15. doi: 10.1007/s12576-015-0379-2. Epub 2015 Apr 18. — View Citation

Bijur PE, Schechter C, Esses D, Chang AK, Gallagher EJ. Intravenous bolus of ultra-low-dose naloxone added to morphine does not enhance analgesia in emergency department patients. J Pain. 2006 Feb;7(2):75-81. doi: 10.1016/j.jpain.2005.08.008. — View Citation

Birnbaum A, Esses D, Bijur PE, Holden L, Gallagher EJ. Randomized double-blind placebo-controlled trial of two intravenous morphine dosages (0.10 mg/kg and 0.15 mg/kg) in emergency department patients with moderate to severe acute pain. Ann Emerg Med. 2007 Apr;49(4):445-53, 453.e1-2. doi: 10.1016/j.annemergmed.2006.06.030. Epub 2006 Sep 15. — View Citation

Chang AK, Bijur PE, Baccelieri A, Gallagher EJ. Efficacy and safety profile of a single dose of hydromorphone compared with morphine in older adults with acute, severe pain: a prospective, randomized, double-blind clinical trial. Am J Geriatr Pharmacother. 2009 Feb;7(1):1-10. doi: 10.1016/j.amjopharm.2009.02.002. — View Citation

Dourish CT, Hawley D, Iversen SD. Enhancement of morphine analgesia and prevention of morphine tolerance in the rat by the cholecystokinin antagonist L-364,718. Eur J Pharmacol. 1988 Mar 15;147(3):469-72. doi: 10.1016/0014-2999(88)90183-5. — View Citation

Ostelo RW, Deyo RA, Stratford P, Waddell G, Croft P, Von Korff M, Bouter LM, de Vet HC. Interpreting change scores for pain and functional status in low back pain: towards international consensus regarding minimal important change. Spine (Phila Pa 1976). 2008 Jan 1;33(1):90-4. doi: 10.1097/BRS.0b013e31815e3a10. — View Citation

Patanwala AE, Keim SM, Erstad BL. Intravenous opioids for severe acute pain in the emergency department. Ann Pharmacother. 2010 Nov;44(11):1800-9. doi: 10.1345/aph.1P438. Epub 2010 Oct 26. — View Citation

Pathan SA, Mitra B, Bhutta ZA, Qureshi I, Spencer E, Hameed AA, Nadeem S, Tahir R, Anjum S, Cameron PA. A comparative, epidemiological study of acute renal colic presentations to emergency departments in Doha, Qatar, and Melbourne, Australia. Int J Emerg Med. 2018 Jan 3;11(1):1. doi: 10.1186/s12245-017-0160-9. — View 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. — View Citation

Terner JM, Barrett AC, Lomas LM, Negus SS, Picker MJ. Influence of low doses of naltrexone on morphine antinociception and morphine tolerance in male and female rats of four strains. Pain. 2006 May;122(1-2):90-101. doi: 10.1016/j.pain.2006.01.019. Epub 2006 Mar 9. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients who have an effective analgesic response (defined as at least a 50% improvement in pain scores) at 120 minutes post-randomization.	Pain scores used are the numerical rating scale (0 low to 10 high) or visual analogue scale (0 low to 100mm high).	120 minutes
Primary	Total dose of opioid received at 120 minutes in patients reporting a reduction in pain scores from baseline.	Dose of opioid measured in mg/kg	120 minutes
Primary	Proportion of patients who require rescue medications at 30 minutes post-randomization.		30 minutes
Secondary	Time to reach effective pain reduction (defined as at least a 50% improvement in pain scores) within 120 minutes of treatment.	Pain scores used are the numerical rating scale (0 low to 10 high) or visual analogue scale (0 low to 100mm high).	120 minutes
Secondary	Subjective effects of the drugs measured by scores on the drug effects questionnaire.	Drug effects questionnaire rates symptoms from 'not at all' at 0mm to 'extremely' at 100mm.	120 minutes