Ambulatory Infusions of Lidocaine and Ketamine for Management of Chronic Pain

NCT04123652 | Completed Phase 4

• 1 other identifier: 16124-11:10:3610-082018
• Study Type: interventional
• Target: 162
• Locations: 1 country
• Sites: 1

Brief Summary

As lidocaine and ketamine provide analgesia by acting on different molecular pathways, administering them together may produce synergistic effects, which can allow for using a lower dose of each medication and thereby reducing the corresponding side effects. To the investigator's knowledge, despite the common practice of multimodal analgesia, lidocaine-ketamine infusions have never been studied prospectively in an out of hospital setting to treat neuropathic pain. The aim of the present study is to evaluate the effectiveness of the current routine practice of lidocaine-ketamine infusions conducted at Allevio Pain Management Clinic, a large outpatient community based chronic pain management facility. Lidocaine-ketamine infusions are prescribed to patients that have pain that is considered to be neuropathic for which standard anti-neuropathic medications have been ineffective or poorly tolerated by patients. A prospective longitudinal study.

Conditions

Chronic Neuropathic Pain and Fibromyalgia

Keywords

Neuropathic pain; Fibromyalgia; Lidocaine infusion; Ketamine infusion; Chronic pain

Outcome Measures

Primary Outcomes (1)

• Evaluation of effectiveness of lidocaine-ketamine infusions: PQAS-R

  Primary outcome measure: relative change on the PQAS-R. Moderate clinically important improvement is considered as 30% reduction (Dworkin et al., 2008)

  4 weeks after the first infusion and every 4 weeks up to 36 weeks

Secondary Outcomes (8)

• Effect of lidocaine and ketamine infusion on BDI

  Baseline to end-of-study every 4 weeks up to 36 weeks

• Effect of lidocaine and ketamine infusion on PGIC

  Baseline to end-of-study every 4 weeks up to 36 weeks

• Effect of lidocaine and ketamine infusion on BPI

  Baseline to end-of-study every 4 weeks up to 36 weeks

• Effect of lidocaine and ketamine infusion on PQAS-R

  Baseline to end-of-study every 4 weeks up to 36 weeks

• Effect of lidocaine and ketamine infusion on PSEQ

  Baseline to end-of-study every 4 weeks up to 36 weeks

Study Arms (1)

Lidocaine and ketamine infusion

OTHER

Drug: Lidocaine Hydrochloride 2% Intravenous Solution, DIN 02421992

Interventions

Lidocaine Hydrochloride 2% Intravenous Solution, DIN 02421992 DRUG

An intravenous will be started. • Lidocaine - initial dose of 5.0 mg/kg +/- 1.0 mg/kg (based on actual weight, up to maximum dose 600 mg) over 45 minutes, followed by increases of 0.5 mg/kg each infusion based on tolerability of side effects, not to exceed 7 mg/kg or 600 mg. • Ketamine - initial dose of 0.1 mg/kg (based on actual weight) over 45 minutes (rounded to nearest 5 mg, up to maximum 15 mg), increased by 0.1 mg/kg (rounded to nearest 5 mg) each infusion based on tolerability of side effects During the infusion patient will be monitored by another MD for BP, PR, PO2. Patients will not be allowed to drive for 24 hours.

Also known as: ketamine Hydrochloride, Serial# 5751304560, DIN 02246796

Lidocaine and ketamine infusion

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pain duration \> 3 months;
• Multifocal and/or non-dermatomal neuropathic pain per Pain Diagram;
• Failed medical management with at least 2 neuromodulation agents (e.g., gabapentinoids, antidepressants, cannabinoids);
• Neuropathic component (12 or more points on S-LANSS);

You may not qualify if:

• Non-English speakers;
• Refusal to sign informed consent;
• Allergy to ketamine and/or lidocaine;
• Known relative contraindications to ketamine use which include poorly controlled systemic illnesses: hypertension, hyperthyroidism, ischemic heart disease, heart failure, psychiatric comorbidity (e.g., psychosis, schizophrenia, dissociative state);
• Known contraindication to lidocaine use which include current symptomatic or clinically significant brady- or tachyarrhythmia, systolic blood pressure \<90 or \>180 mmHg;
• Scheduled interventions targeting neuropathic pain: epidural injections, peripheral nerve blocks, Bier block, radiofrequency of dorsal root ganglia and peripheral nerves, additional lidocaine or ketamine infusions;
• Newly added analgesic or neuromodulating medications within 30 days;
• Recently performed neuromodulating interventions within 90 days;
• Previous lidocaine-ketamine, lidocaine or ketamine infusion within 6 months;
• Acute intoxication or active illegal substance abuse;

Sponsors & Collaborators

• Allevio Pain Management Clinic: lead

Study Sites (1)

Allevio Pain Management Clinic

Toronto, Ontario, M3B 3S6, Canada

Location

Related Publications (19)

• Dworkin RH, Turk DC, Wyrwich KW, Beaton D, Cleeland CS, Farrar JT, Haythornthwaite JA, Jensen MP, Kerns RD, Ader DN, Brandenburg N, Burke LB, Cella D, Chandler J, Cowan P, Dimitrova R, Dionne R, Hertz S, Jadad AR, Katz NP, Kehlet H, Kramer LD, Manning DC, McCormick C, McDermott MP, McQuay HJ, Patel S, Porter L, Quessy S, Rappaport BA, Rauschkolb C, Revicki DA, Rothman M, Schmader KE, Stacey BR, Stauffer JW, von Stein T, White RE, Witter J, Zavisic S. Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations. J Pain. 2008 Feb;9(2):105-21. doi: 10.1016/j.jpain.2007.09.005. Epub 2007 Dec 11.

  PMID: 18055266 BACKGROUND

• BONICA JJ. The management of pain of cancer. J Mich State Med Soc. 1953 Mar;52(3):284-90. No abstract available.

  PMID: 13035388 RESULT

• Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, Shibuya K, Salomon JA, Abdalla S, Aboyans V, Abraham J, Ackerman I, Aggarwal R, Ahn SY, Ali MK, Alvarado M, Anderson HR, Anderson LM, Andrews KG, Atkinson C, Baddour LM, Bahalim AN, Barker-Collo S, Barrero LH, Bartels DH, Basanez MG, Baxter A, Bell ML, Benjamin EJ, Bennett D, Bernabe E, Bhalla K, Bhandari B, Bikbov B, Bin Abdulhak A, Birbeck G, Black JA, Blencowe H, Blore JD, Blyth F, Bolliger I, Bonaventure A, Boufous S, Bourne R, Boussinesq M, Braithwaite T, Brayne C, Bridgett L, Brooker S, Brooks P, Brugha TS, Bryan-Hancock C, Bucello C, Buchbinder R, Buckle G, Budke CM, Burch M, Burney P, Burstein R, Calabria B, Campbell B, Canter CE, Carabin H, Carapetis J, Carmona L, Cella C, Charlson F, Chen H, Cheng AT, Chou D, Chugh SS, Coffeng LE, Colan SD, Colquhoun S, Colson KE, Condon J, Connor MD, Cooper LT, Corriere M, Cortinovis M, de Vaccaro KC, Couser W, Cowie BC, Criqui MH, Cross M, Dabhadkar KC, Dahiya M, Dahodwala N, Damsere-Derry J, Danaei G, Davis A, De Leo D, Degenhardt L, Dellavalle R, Delossantos A, Denenberg J, Derrett S, Des Jarlais DC, Dharmaratne SD, Dherani M, Diaz-Torne C, Dolk H, Dorsey ER, Driscoll T, Duber H, Ebel B, Edmond K, Elbaz A, Ali SE, Erskine H, Erwin PJ, Espindola P, Ewoigbokhan SE, Farzadfar F, Feigin V, Felson DT, Ferrari A, Ferri CP, Fevre EM, Finucane MM, Flaxman S, Flood L, Foreman K, Forouzanfar MH, Fowkes FG, Franklin R, Fransen M, Freeman MK, Gabbe BJ, Gabriel SE, Gakidou E, Ganatra HA, Garcia B, Gaspari F, Gillum RF, Gmel G, Gosselin R, Grainger R, Groeger J, Guillemin F, Gunnell D, Gupta R, Haagsma J, Hagan H, Halasa YA, Hall W, Haring D, Haro JM, Harrison JE, Havmoeller R, Hay RJ, Higashi H, Hill C, Hoen B, Hoffman H, Hotez PJ, Hoy D, Huang JJ, Ibeanusi SE, Jacobsen KH, James SL, Jarvis D, Jasrasaria R, Jayaraman S, Johns N, Jonas JB, Karthikeyan G, Kassebaum N, Kawakami N, Keren A, Khoo JP, King CH, Knowlton LM, Kobusingye O, Koranteng A, Krishnamurthi R, Lalloo R, Laslett LL, Lathlean T, Leasher JL, Lee YY, Leigh J, Lim SS, Limb E, Lin JK, Lipnick M, Lipshultz SE, Liu W, Loane M, Ohno SL, Lyons R, Ma J, Mabweijano J, MacIntyre MF, Malekzadeh R, Mallinger L, Manivannan S, Marcenes W, March L, Margolis DJ, Marks GB, Marks R, Matsumori A, Matzopoulos R, Mayosi BM, McAnulty JH, McDermott MM, McGill N, McGrath J, Medina-Mora ME, Meltzer M, Mensah GA, Merriman TR, Meyer AC, Miglioli V, Miller M, Miller TR, Mitchell PB, Mocumbi AO, Moffitt TE, Mokdad AA, Monasta L, Montico M, Moradi-Lakeh M, Moran A, Morawska L, Mori R, Murdoch ME, Mwaniki MK, Naidoo K, Nair MN, Naldi L, Narayan KM, Nelson PK, Nelson RG, Nevitt MC, Newton CR, Nolte S, Norman P, Norman R, O'Donnell M, O'Hanlon S, Olives C, Omer SB, Ortblad K, Osborne R, Ozgediz D, Page A, Pahari B, Pandian JD, Rivero AP, Patten SB, Pearce N, Padilla RP, Perez-Ruiz F, Perico N, Pesudovs K, Phillips D, Phillips MR, Pierce K, Pion S, Polanczyk GV, Polinder S, Pope CA 3rd, Popova S, Porrini E, Pourmalek F, Prince M, Pullan RL, Ramaiah KD, Ranganathan D, Razavi H, Regan M, Rehm JT, Rein DB, Remuzzi G, Richardson K, Rivara FP, Roberts T, Robinson C, De Leon FR, Ronfani L, Room R, Rosenfeld LC, Rushton L, Sacco RL, Saha S, Sampson U, Sanchez-Riera L, Sanman E, Schwebel DC, Scott JG, Segui-Gomez M, Shahraz S, Shepard DS, Shin H, Shivakoti R, Singh D, Singh GM, Singh JA, Singleton J, Sleet DA, Sliwa K, Smith E, Smith JL, Stapelberg NJ, Steer A, Steiner T, Stolk WA, Stovner LJ, Sudfeld C, Syed S, Tamburlini G, Tavakkoli M, Taylor HR, Taylor JA, Taylor WJ, Thomas B, Thomson WM, Thurston GD, Tleyjeh IM, Tonelli M, Towbin JA, Truelsen T, Tsilimbaris MK, Ubeda C, Undurraga EA, van der Werf MJ, van Os J, Vavilala MS, Venketasubramanian N, Wang M, Wang W, Watt K, Weatherall DJ, Weinstock MA, Weintraub R, Weisskopf MG, Weissman MM, White RA, Whiteford H, Wiersma ST, Wilkinson JD, Williams HC, Williams SR, Witt E, Wolfe F, Woolf AD, Wulf S, Yeh PH, Zaidi AK, Zheng ZJ, Zonies D, Lopez AD, Murray CJ, AlMazroa MA, Memish ZA. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012 Dec 15;380(9859):2163-96. doi: 10.1016/S0140-6736(12)61729-2.

  PMID: 23245607 RESULT

• IASP. (2003). How Prevalent Is Chronic Pain? International Association for the Study of Pain. Retrieved from https://www.iasp-pain.org/files/Content/ContentFolders/Publications2/PainClinicalUpdates/Archives/PCU03-2_1390265045864_38.pdf

  RESULT

• Goldberg DS, McGee SJ. Pain as a global public health priority. BMC Public Health. 2011 Oct 6;11:770. doi: 10.1186/1471-2458-11-770.

  PMID: 21978149 RESULT

• Cho SK, Heiby EM, McCracken LM, Moon DE, Lee JH. Daily functioning in chronic pain: study of structural relations with posttraumatic stress disorder symptoms, pain intensity, and pain avoidance. Korean J Pain. 2011 Mar;24(1):13-21. doi: 10.3344/kjp.2011.24.1.13. Epub 2011 Feb 25.

  PMID: 21390174 RESULT

• Wahl AK, Rustoen T, Rokne B, Lerdal A, Knudsen O, Miaskowski C, Moum T. The complexity of the relationship between chronic pain and quality of life: a study of the general Norwegian population. Qual Life Res. 2009 Oct;18(8):971-80. doi: 10.1007/s11136-009-9515-x. Epub 2009 Aug 18.

  PMID: 19688608 RESULT

• Gaskin DJ, Richard P. The economic costs of pain in the United States. J Pain. 2012 Aug;13(8):715-24. doi: 10.1016/j.jpain.2012.03.009. Epub 2012 May 16.

  PMID: 22607834 RESULT

• Fitzcharles MA, Baerwald C, Ablin J, Hauser W. Efficacy, tolerability and safety of cannabinoids in chronic pain associated with rheumatic diseases (fibromyalgia syndrome, back pain, osteoarthritis, rheumatoid arthritis): A systematic review of randomized controlled trials. Schmerz. 2016 Feb;30(1):47-61. doi: 10.1007/s00482-015-0084-3.

  PMID: 26767993 RESULT

• Ballantyne JC, Mao J. Opioid therapy for chronic pain. N Engl J Med. 2003 Nov 13;349(20):1943-53. doi: 10.1056/NEJMra025411. No abstract available.

  PMID: 14614170 RESULT

• Noble M, Treadwell JR, Tregear SJ, Coates VH, Wiffen PJ, Akafomo C, Schoelles KM. Long-term opioid management for chronic noncancer pain. Cochrane Database Syst Rev. 2010 Jan 20;2010(1):CD006605. doi: 10.1002/14651858.CD006605.pub2.

  PMID: 20091598 RESULT

• IASP. (1994). Part III: Pain Terms, A Current List with Definitions and Notes on Usage. In Classification of Chronic Pain (second ed., pp. 209-214): IASP Press. Retrieved from

  RESULT

• van Hecke O, Austin SK, Khan RA, Smith BH, Torrance N. Neuropathic pain in the general population: a systematic review of epidemiological studies. Pain. 2014 Apr;155(4):654-662. doi: 10.1016/j.pain.2013.11.013. Epub 2013 Nov 26.

  PMID: 24291734 RESULT

• Campbell, J. N., & Meyer, R. A. (2006). Mechanisms of neuropathic pain. Neuron, 52(1), 77-92. doi:10.1016/j.neuron.2006.09.021 CDC. (2017a). Opioid Overdose. Centers for Disease Control and Prevention. Retrieved from https://www.cdc.gov/drugoverdose/index.html CDC. (2017b). Prescribing Data. Centers for Disease Control and Prevention. Retrieved from https://www.cdc.gov/drugoverdose/data/prescribing.html

  RESULT

• Gilron I, Watson CP, Cahill CM, Moulin DE. Neuropathic pain: a practical guide for the clinician. CMAJ. 2006 Aug 1;175(3):265-75. doi: 10.1503/cmaj.060146.

  PMID: 16880448 RESULT

• Niesters M, Martini C, Dahan A. Ketamine for chronic pain: risks and benefits. Br J Clin Pharmacol. 2014 Feb;77(2):357-67. doi: 10.1111/bcp.12094.

  PMID: 23432384 RESULT

• Dale R, Stacey B. Multimodal Treatment of Chronic Pain. Med Clin North Am. 2016 Jan;100(1):55-64. doi: 10.1016/j.mcna.2015.08.012. Epub 2015 Oct 17.

  PMID: 26614719 RESULT

• Rogers M, Tang L, Madge DJ, Stevens EB. The role of sodium channels in neuropathic pain. Semin Cell Dev Biol. 2006 Oct;17(5):571-81. doi: 10.1016/j.semcdb.2006.10.009. Epub 2006 Oct 28.

  PMID: 17123847 RESULT

• Zhou HY, Chen SR, Pan HL. Targeting N-methyl-D-aspartate receptors for treatment of neuropathic pain. Expert Rev Clin Pharmacol. 2011 May;4(3):379-88. doi: 10.1586/ecp.11.17.

  PMID: 21686074 RESULT

MeSH Terms

Conditions

Fibromyalgia; Neuralgia; Chronic Pain

Interventions

Lidocaine; Ketamine

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Neuromuscular Diseases; Nervous System Diseases; Peripheral Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Ramin Safakish, MD.FRCPC

  Allevio Pain Management Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients are assessed for eligibility on their first visit (screening visit); additional visits may be required to address patient questions and collect baseline data. Qualified participants will be scheduled for their 5 infusions at 8 week intervals. Dosing and infusion orders are completed by one of the physician-investigators prior to patient arrival based on body weight, and modified if required after individual evaluation. Based on published literature and clinical impression, higher doses seem to be more effective and result in longer pain relief. Therefore, subsequent infusion doses will be increased to the maximally tolerated doses (i.e. minimal side effects). Participants will be asked to complete the follow-up questionnaires every four weeks starting from their first infusion up to 8 times. On their last study visit, 4 weeks following the last infusion, participants will have an exit interview in addition to completing study measures.

Study Record Dates

• First Submitted: October 9, 2019
• First Posted: October 11, 2019
• Study Start: November 5, 2017
• Primary Completion: November 11, 2020
• Study Completion: November 11, 2020
• Last Updated: December 4, 2020

Record last verified: 2017-11

Locations

CA (1)