Analgesic Effects of Perioperative Propranolol Administration for Spine Surgery

Degenerative Disc Disease Clinical Trial

Official title:

Analgesic Effects of Perioperative Propranolol Administration for Spine Surgery

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04421209
• Other study ID #: Pro00103364
• Status: Withdrawn
• Phase: Phase 2
• Start date: December 2020
• Est. completion date: September 30, 2021

Study information

• Verified date: March 2021
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine if treatment with low-dose oral propranolol in the days before and after surgery decrease postoperative pain and improve pain scores.

Description:

This study is a randomized, double-blind, placebo controlled clinical trial.The main purpose of this study is to determine if postsurgical opioid use and pain scores are decreased with oral Propranolol treatment. The treatment period will last for six days and the observation period will last for three months. Effectiveness of treatment will be assessed by means of post-operative opioid consumption as primary outcome measure.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: September 30, 2021
• Est. primary completion date: June 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or female patients age >18 undergoing elective spinal fusion surgery, with plans to remain inpatient for = 48hrs and receive IV or oral opioids;

• Females of child bearing potential must test negative on a pregnancy test at Visit 1 and utilize acceptable means of birth control for the duration of the study;

• Patients must be judged by the study team to be likely to be reliable and to agree to keep all appointments for clinic visits, tests, and procedures required by the protocol;

• Patients must have the ability to fully participate in the informed consent process.

Exclusion Criteria:

• Disease-related: History of exercise- or exertion-induced asthma or current treatments for asthma; Unstable medical or neurological illness; Heart block greater than first degree (EKG); History of coronary artery disease, or history of congestive heart failure; Baseline heart rate or blood pressure that in the opinion of the investigator would constitute too great a risk when considered in the context of the patient's medical comorbidities and health history; Significant suicidal or homicidal ideation, or current DSM-IV diagnosis of bipolar disorder, schizophrenia or other psychotic disorder, or cognitive disorder due to a general medical condition; History of diabetes

• Exposure-related: History of ß-blocker use within six months of enrollment in the trial; Total baseline preoperative opioid consumption greater than 50 oral milligram morphine equivalents (MME) per day; Current use or use within the past two weeks of methadone, levorphanol, buprenorphine, butorphanol, pentazocine, tramadol, nalbuphine, naloxone, or naltrexone.

• Patient characteristics: Female patients who are pregnant or breast-feeding; Known allergy to study medication; Alcohol/substance abuse within past six months; Ongoing or anticipated disability compensation or litigation issues, in the best judgement of the investigator; Presence of any factors/conditions, medical or other, that in the judgment of the investigator may interfere with performance of study outcome measures, such as treatment-refractory history; Non-ambulatory or require the use of crutches or a walker; No access to a telephone

Related Conditions & MeSH terms

• Degenerative Disc Disease
• Intervertebral Disc Degeneration
• Lumbar Disc Disease
• Spinal Diseases
• Spinal Fusion

Intervention

Drug:
• Propranolol Hcl 40mg Tab
40mg PO BID for the three days prior to surgery, 40mg PO BID the day of surgery and on post-op days 1 and 2.
• Placebo oral tablet
Placebo tablets administered with the same schedule of Propranolol tablets

Locations

Country	Name	City	State
United States	Duke University Hospital	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Duke University	Foundation for Anesthesia Education and Research

Country where clinical trial is conducted

United States, 

References & Publications (13)

Afify EA, Andijani NM. Potentiation of Morphine-Induced Antinociception by Propranolol: The Involvement of Dopamine and GABA Systems. Front Pharmacol. 2017 Nov 10;8:794. doi: 10.3389/fphar.2017.00794. eCollection 2017. — View Citation

Ciszek BP, O'Buckley SC, Nackley AG. Persistent Catechol-O-methyltransferase-dependent Pain Is Initiated by Peripheral ß-Adrenergic Receptors. Anesthesiology. 2016 May;124(5):1122-35. doi: 10.1097/ALN.0000000000001070. — View Citation

Gan TJ, Habib AS, Miller TE, White W, Apfelbaum JL. Incidence, patient satisfaction, and perceptions of post-surgical pain: results from a US national survey. Curr Med Res Opin. 2014 Jan;30(1):149-60. doi: 10.1185/03007995.2013.860019. Epub 2013 Nov 15. Review. — View Citation

Hartung JE, Ciszek BP, Nackley AG. ß2- and ß3-adrenergic receptors drive COMT-dependent pain by increasing production of nitric oxide and cytokines. Pain. 2014 Jul;155(7):1346-1355. doi: 10.1016/j.pain.2014.04.011. Epub 2014 Apr 13. — View Citation

Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet. 2006 May 13;367(9522):1618-25. Review. — View Citation

Krebs EE, Lorenz KA, Bair MJ, Damush TM, Wu J, Sutherland JM, Asch SM, Kroenke K. Development and initial validation of the PEG, a three-item scale assessing pain intensity and interference. J Gen Intern Med. 2009 Jun;24(6):733-8. doi: 10.1007/s11606-009-0981-1. Epub 2009 May 6. — View Citation

Light KC, Bragdon EE, Grewen KM, Brownley KA, Girdler SS, Maixner W. Adrenergic dysregulation and pain with and without acute beta-blockade in women with fibromyalgia and temporomandibular disorder. J Pain. 2009 May;10(5):542-52. doi: 10.1016/j.jpain.2008.12.006. — View Citation

Nackley AG, Tan KS, Fecho K, Flood P, Diatchenko L, Maixner W. Catechol-O-methyltransferase inhibition increases pain sensitivity through activation of both beta2- and beta3-adrenergic receptors. Pain. 2007 Apr;128(3):199-208. doi: 10.1016/j.pain.2006.09.022. Epub 2006 Nov 7. — View Citation

Pagé MG, Kudrina I, Zomahoun HTV, Ziegler D, Beaulieu P, Charbonneau C, Cogan J, Daoust R, Martel MO, Néron A, Richebé P, Clarke H. Relative frequency and risk factors for long-term opioid therapy following surgery and trauma among adults: a systematic review protocol. Syst Rev. 2018 Jul 18;7(1):97. doi: 10.1186/s13643-018-0760-3. Review. — View Citation

Stanley TH, de Lange S, Boscoe MJ, de Bruijn N. The influence of chronic preoperative propranolol therapy on cardiovascular dynamics and narcotic requirements during operation in patients with coronary artery disease. Can Anaesth Soc J. 1982 Jul;29(4):319-24. — View Citation

Tchivileva IE, Lim PF, Smith SB, Slade GD, Diatchenko L, McLean SA, Maixner W. Effect of catechol-O-methyltransferase polymorphism on response to propranolol therapy in chronic musculoskeletal pain: a randomized, double-blind, placebo-controlled, crossover pilot study. Pharmacogenet Genomics. 2010 Apr;20(4):239-48. doi: 10.1097/FPC.0b013e328337f9ab. — View Citation

Teimoori, B., Khoshfetrat, M., Beyrami, F., Sakhavar, N., Dehbashi, Z., Narouie, B., & Davarian, A. Propranolol decreases the post-operative pain and analgesic administration following abdominal hysterectomy. Life Sciences Journal 9: 1216-1220, 2012.

Zanelatto FB, Dias EV, Teixeira JM, Sartori CR, Parada CA, Tambeli CH. Anti-inflammatory effects of propranolol in the temporomandibular joint of female rats and its contribution to antinociceptive action. Eur J Pain. 2018 Mar;22(3):572-582. doi: 10.1002/ejp.1143. Epub 2017 Dec 11. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Acute postoperative opioid use at 24 hours	Total opioid use from 0 to 24 hours post-op will be quantified. Opioid doses administered via all routes will be converted to standard oral morphine equivalents (OME).	24 hours postoperatively
Secondary	Acute postoperative opioid use at 48 hours	Total opioid use from 24 to 48 hours post-op will be quantified. Opioid doses administered via all routes will be converted to standard oral morphine equivalents (OME).	48 hours postoperatively
Secondary	Sub-acute postoperative opioid use at 1 week	Patient reported current opioid use for the prior 24 hours will be quantified at 1 week post-op. Opioid use will be converted to standard oral morphine equivalents (OME).	1 week postoperatively
Secondary	Sub-acute postoperative opioid use at 4 weeks	Patient reported current opioid use for the prior 24 hours will be quantified at 4 weeks post-op. Opioid use will be converted to standard oral morphine equivalents (OME).	4 weeks postoperatively
Secondary	Sub-acute postoperative opioid use at 12 weeks	Patient reported current opioid use for the prior 24 hours will be quantified at 12 weeks post-op. Opioid use will be converted to standard oral morphine equivalents (OME).	12 weeks postoperatively
Secondary	Acute postoperative pain scores at 24 hours	The CDC recommended 3-item Scale for Assessing Pain Intensity and Interference (PEG) will be used to assess postoperative pain over the past 24 hours. These data will be obtained at 24 post-op. The score is reported on a scale from 0 to 30. A higher score indicates more pain and therefore a worse outcome.	24 hours post-op
Secondary	Acute postoperative pain scores at 48 hours	The CDC recommended 3-item Scale for Assessing Pain Intensity and Interference (PEG) will be used to assess postoperative pain over the past 24 hours. These data will be obtained at 48 hours post-op. The score is reported on a scale from 0 to 30. A higher score indicates more pain and therefore a worse outcome.	48 hours post-op
Secondary	Sub-acute postoperative pain scores at 1 week	The CDC recommended 3-item Scale for Assessing Pain Intensity and Interference (PEG) will be used to assess postoperative pain over the past 24 hours. These data will be obtained at 1 week post-op. The score is reported on a scale from 0 to 30. A higher score indicates more pain and therefore a worse outcome.	1 week postoperatively
Secondary	Sub-acute postoperative pain scores at 4 weeks	The CDC recommended 3-item Scale for Assessing Pain Intensity and Interference (PEG) will be used to assess postoperative pain over the past 24 hours. These data will be obtained at 4 week post-op. The score is reported on a scale from 0 to 30. A higher score indicates more pain and therefore a worse outcome.	4 weekspostoperatively
Secondary	Sub-acute postoperative pain scores at 12 weeks	The CDC recommended 3-item Scale for Assessing Pain Intensity and Interference (PEG) will be used to assess postoperative pain over the past 24 hours. These data will be obtained at 12 weeks post-op. The score is reported on a scale from 0 to 30. A higher score indicates more pain and therefore a worse outcome.	12 weeks postoperatively