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Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT02455726
Other study ID # 1601 gluta-aos
Secondary ID
Status Not yet recruiting
Phase N/A
First received April 23, 2015
Last updated May 25, 2015
Start date September 2015
Est. completion date December 2017

Study information

Verified date May 2015
Source Azienda Ospedaliera Spedali Civili di Brescia
Contact Monica A Venturini, Doctor
Email monica.venturini@spedalicivili.brescia.it
Is FDA regulated No
Health authority Italy: Ethics Committee
Study type Interventional

Clinical Trial Summary

Magnesium exerts analgesic effects in several animal pain models and in patients affected by acute postoperative pain and chronic pain of neuropathic origin. There is no evidence that magnesium can modulate pain in patients with peripheral arterial occlusive disease (PAOD).

We describe the protocol of a single-center randomized double-blind clinical trial aimed at assessing the efficacy of oral magnesium supplementation in controlling severe pain in patients with advanced PAOD.


Description:

- Adult patients admitted to our Acute Pain Service for intractable pain will be eligible if they are affected by PAOD at stages III and IV of Lèriche-Fontaine classification, and are opioid-naïve.

- Patients enrolled will be randomized to the control group, treated with standard therapy, consisting of an oral administration of oxycodone 5 mg and pregabalin 25 mg per day plus placebo (fructose 10 g) twice a day for two weeks, or to the experimental group, treated with magnesium oxide 300 mg twice a day.

- Randomization will be computer-generated, with allocation concealment obtained using opaque, sequentially numbered and sealed envelopes. Trials participants, care providers, data collectors, outcome assessors and data analysts will be blinded to treatment allocation.

- Patients will be evaluated on the day of hospital admission (day 0) and on days 2, 4, 6, 8, 12, and 14 with the following information being collected: daily oxycodone dose received; patient's perceived average and maximum pain using the Numerical Rating Scale (NRS: 0=no pain to 10=worst possible pain); pain relief using Pain Relief Scale (PRS: 0% no pain relief to 100% complete pain relief); characteristics of the pain, using the Neuropathic Pain Scale (NPS: 10 items); impact of pain on the patient's daily activities, using the Brief Pain Inventory (BPI; 9 items).

- A sample size calculation performed for the primary outcome showed that 150 patients (75 per group) are needed to achieve 90% power to detect a minimum reduction of 30% in oxycodone dosage in the experimental group, after allowing for a drop-out rate of around 20%.

- Ethical approval of the study protocol has been obtained from Comitato Etico Provinciale di Brescia, Brescia, Italy.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 150
Est. completion date December 2017
Est. primary completion date December 2017
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility Inclusion Criteria:

- adult patients (18 years or above)

- PAOD at stages III and IV according to the Lèriche-Fontaine classification

- no treatment with opioids at the time of recruitment

Exclusion Criteria:

- renal failure (serum creatinine = 2.0 mg/dl);

- congestive heart failure (New York Heart Association, NYHA > 3);

- treatment with digoxin and/or calcium channel blockers;

- pre-existing neuromuscular diseases;

- chronic diarrhea;

- acute limb ischemia successfully treated with interventional angiography, Fogarty embolectomy and/or surgical revascularization.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment


Intervention

Dietary Supplement:
Magnesium oxide
Oral magnesium oxide 300 mg twice a day
Fructose
Oral fructose 10 g twice a day
Drug:
Oxycodone
Oxycodone hydrochloride 5 mg at 8 am
Pregabalin
Pregabalin 25 mg at 8 pm

Locations

Country Name City State
n/a

Sponsors (1)

Lead Sponsor Collaborator
Azienda Ospedaliera Spedali Civili di Brescia

References & Publications (47)

Albrecht E, Kirkham KR, Liu SS, Brull R. Peri-operative intravenous administration of magnesium sulphate and postoperative pain: a meta-analysis. Anaesthesia. 2013 Jan;68(1):79-90. doi: 10.1111/j.1365-2044.2012.07335.x. Epub 2012 Nov 1. Review. — View Citation

Begon S, Pickering G, Eschalier A, Dubray C. Magnesium increases morphine analgesic effect in different experimental models of pain. Anesthesiology. 2002 Mar;96(3):627-32. — View Citation

Benyamin R, Trescot AM, Datta S, Buenaventura R, Adlaka R, Sehgal N, Glaser SE, Vallejo R. Opioid complications and side effects. Pain Physician. 2008 Mar;11(2 Suppl):S105-20. Review. — View Citation

Bondok RS, Abd El-Hady AM. Intra-articular magnesium is effective for postoperative analgesia in arthroscopic knee surgery. Br J Anaesth. 2006 Sep;97(3):389-92. Epub 2006 Jul 11. — View Citation

Bonezzi C, Nava A, Barbieri M, Bettaglio R, Demartini L, Miotti D, Paulin L. [Validazione della versione italiana del Brief Pain Inventory nei pazienti con dolore cronico]. Minerva Anestesiol. 2002 Jul-Aug;68(7-8):607-11. Italian. — View Citation

Borazan H, Kececioglu A, Okesli S, Otelcioglu S. Oral magnesium lozenge reduces postoperative sore throat: a randomized, prospective, placebo-controlled study. Anesthesiology. 2012 Sep;117(3):512-8. doi: 10.1097/ALN.0b013e3182639d5f. — View Citation

Brill S, Sedgwick PM, Hamann W, Di Vadi PP. Efficacy of intravenous magnesium in neuropathic pain. Br J Anaesth. 2002 Nov;89(5):711-4. — View Citation

Bujalska M, Makulska-Nowak H, Gumulka SW. Magnesium ions and opioid agonists in vincristine-induced neuropathy. Pharmacol Rep. 2009 Nov-Dec;61(6):1096-104. — View Citation

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Chen Y, Zhang Y, Zhu YL, Fu PL. Efficacy and safety of an intra-operative intra-articular magnesium/ropivacaine injection for pain control following total knee arthroplasty. J Int Med Res. 2009 Nov-Dec;37(6):1733-41. Corrected and republished in: J Int Med Res. 2012;40(5):2032-40. Retraction in: J Int Med Res. 2012;40(5):2031. — View Citation

Cizmeci P, Ozkose Z. Magnesium sulphate as an adjuvant to total intravenous anesthesia in septorhinoplasty: a randomized controlled study. Aesthetic Plast Surg. 2007 Mar-Apr;31(2):167-73. — View Citation

Crosby V, Wilcock A, Corcoran R. The safety and efficacy of a single dose (500 mg or 1 g) of intravenous magnesium sulfate in neuropathic pain poorly responsive to strong opioid analgesics in patients with cancer. J Pain Symptom Manage. 2000 Jan;19(1):35-9. — View Citation

De Kock MF, Lavand'homme PM. The clinical role of NMDA receptor antagonists for the treatment of postoperative pain. Best Pract Res Clin Anaesthesiol. 2007 Mar;21(1):85-98. Review. — View Citation

Dowell D, Kunins HV, Farley TA. Opioid analgesics--risky drugs, not risky patients. JAMA. 2013 Jun 5;309(21):2219-20. doi: 10.1001/jama.2013.5794. — View Citation

Felsby S, Nielsen J, Arendt-Nielsen L, Jensen TS. NMDA receptor blockade in chronic neuropathic pain: a comparison of ketamine and magnesium chloride. Pain. 1996 Feb;64(2):283-91. — View Citation

Fisher K, Coderre TJ, Hagen NA. Targeting the N-methyl-D-aspartate receptor for chronic pain management. Preclinical animal studies, recent clinical experience and future research directions. J Pain Symptom Manage. 2000 Nov;20(5):358-73. Review. — View Citation

FONTAINE R, KIENY R, GANGLOFF JM, CUNY A, SUHLER A, GONZALES I, PARAMODIAZ M. LONG-TERM RESULTS OF RESTORATIVE ARTERIAL SURGERY IN OBSTRUCTIVE DISEASES OF THE ARTERIES. J Cardiovasc Surg (Torino). 1964 Nov-Dec;5:463-72. — View Citation

Fowkes FG, Rudan D, Rudan I, Aboyans V, Denenberg JO, McDermott MM, Norman PE, Sampson UK, Williams LJ, Mensah GA, Criqui MH. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis. Lancet. 2013 Oct 19;382(9901):1329-40. doi: 10.1016/S0140-6736(13)61249-0. Epub 2013 Aug 1. Review. — View Citation

Frampton CL, Hughes-Webb P. The measurement of pain. Clin Oncol (R Coll Radiol). 2011 Aug;23(6):381-6. doi: 10.1016/j.clon.2011.04.008. Epub 2011 May 14. Review. — View Citation

Galer BS, Jensen MP. Development and preliminary validation of a pain measure specific to neuropathic pain: the Neuropathic Pain Scale. Neurology. 1997 Feb;48(2):332-8. — View Citation

Hasanein P, Parviz M, Keshavarz M, Javanmardi K, Mansoori M, Soltani N. Oral magnesium administration prevents thermal hyperalgesia induced by diabetes in rats. Diabetes Res Clin Pract. 2006 Jul;73(1):17-22. Epub 2006 Jan 18. — View Citation

Hewitt DJ. The use of NMDA-receptor antagonists in the treatment of chronic pain. Clin J Pain. 2000 Jun;16(2 Suppl):S73-9. Review. — View Citation

Iseri LT, French JH. Magnesium: nature's physiologic calcium blocker. Am Heart J. 1984 Jul;108(1):188-93. Review. — View Citation

Kew JN, Kemp JA. Ionotropic and metabotropic glutamate receptor structure and pharmacology. Psychopharmacology (Berl). 2005 Apr;179(1):4-29. Epub 2005 Feb 25. Review. Erratum in: Psychopharmacology (Berl). 2005 Oct;182(2):320. — View Citation

Kroin JS, McCarthy RJ, Von Roenn N, Schwab B, Tuman KJ, Ivankovich AD. Magnesium sulfate potentiates morphine antinociception at the spinal level. Anesth Analg. 2000 Apr;90(4):913-7. — View Citation

Lysakowski C, Dumont L, Czarnetzki C, Tramèr MR. Magnesium as an adjuvant to postoperative analgesia: a systematic review of randomized trials. Anesth Analg. 2007 Jun;104(6):1532-9, table of contents. Review. — View Citation

Mikkelsen S, Dirks J, Fabricius P, Petersen KL, Rowbotham MC, Dahl JB. Effect of intravenous magnesium on pain and secondary hyperalgesia associated with the heat/capsaicin sensitization model in healthy volunteers. Br J Anaesth. 2001 Jun;86(6):871-3. — View Citation

Murck H. Ketamine, magnesium and major depression--from pharmacology to pathophysiology and back. J Psychiatr Res. 2013 Jul;47(7):955-65. doi: 10.1016/j.jpsychires.2013.02.015. Epub 2013 Mar 26. Review. — View Citation

Nechifor M. Magnesium in major depression. Magnes Res. 2009 Sep;22(3):163S-166S. Review. — View Citation

Nechifor M. Magnesium involvement in pain. Magnes Res. 2011 Dec;24(4):220-2. doi: 10.1684/mrh.2011.0296. — View Citation

Negri E, Bettaglio R, Demartini L, Allegri M, Barbieri M, Miotti D, Paulin L, Buonocore M, Bonezzi C. [Validation of the Italian version of the "Neuropathic Pain Scale" and its clinical applications]. Minerva Anestesiol. 2002 Mar;68(3):95-104. Italian. — View Citation

Petrenko AB, Yamakura T, Baba H, Shimoji K. The role of N-methyl-D-aspartate (NMDA) receptors in pain: a review. Anesth Analg. 2003 Oct;97(4):1108-16. Review. — View Citation

Pickering G, Morel V, Simen E, Cardot JM, Moustafa F, Delage N, Picard P, Eschalier S, Boulliau S, Dubray C. Oral magnesium treatment in patients with neuropathic pain: a randomized clinical trial. Magnes Res. 2011 Jun;24(2):28-35. doi: 10.1684/mrh.2011.0282. — View Citation

Recio-Pinto E, Castillo C. Peripheral N-methyl-D-aspartate receptors as possible targets for chronic pain treatment. Techniques in Reg Anesth & Pain Manag 2010;14:48-58

Rondón LJ, Privat AM, Daulhac L, Davin N, Mazur A, Fialip J, Eschalier A, Courteix C. Magnesium attenuates chronic hypersensitivity and spinal cord NMDA receptor phosphorylation in a rat model of diabetic neuropathic pain. J Physiol. 2010 Nov 1;588(Pt 21):4205-15. doi: 10.1113/jphysiol.2010.197004. — View Citation

Rüger LJ, Irnich D, Abahji TN, Crispin A, Hoffmann U, Lang PM. Characteristics of chronic ischemic pain in patients with peripheral arterial disease. Pain. 2008 Sep 30;139(1):201-8. doi: 10.1016/j.pain.2008.03.027. Epub 2008 May 9. — View Citation

Ryu JH, Kang MH, Park KS, Do SH. Effects of magnesium sulphate on intraoperative anaesthetic requirements and postoperative analgesia in gynaecology patients receiving total intravenous anaesthesia. Br J Anaesth. 2008 Mar;100(3):397-403. doi: 10.1093/bja/aem407. — View Citation

Seyhan TO, Tugrul M, Sungur MO, Kayacan S, Telci L, Pembeci K, Akpir K. Effects of three different dose regimens of magnesium on propofol requirements, haemodynamic variables and postoperative pain relief in gynaecological surgery. Br J Anaesth. 2006 Feb;96(2):247-52. Epub 2005 Nov 25. — View Citation

Shechter M, Bairey Merz CN, Stuehlinger HG, Slany J, Pachinger O, Rabinowitz B. Effects of oral magnesium therapy on exercise tolerance, exercise-induced chest pain, and quality of life in patients with coronary artery disease. Am J Cardiol. 2003 Mar 1;91(5):517-21. — View Citation

Song JW, Lee YW, Yoon KB, Park SJ, Shim YH. Magnesium sulfate prevents remifentanil-induced postoperative hyperalgesia in patients undergoing thyroidectomy. Anesth Analg. 2011 Aug;113(2):390-7. doi: 10.1213/ANE.0b013e31821d72bc. Epub 2011 May 19. — View Citation

Suresh S, Lozono S, Hall SC. Large-dose intravenous methotrexate-induced cutaneous toxicity: can oral magnesium oxide reduce pain? Anesth Analg. 2003 May;96(5):1413-4, table of contents. — View Citation

Tramer MR, Schneider J, Marti RA, Rifat K. Role of magnesium sulfate in postoperative analgesia. Anesthesiology. 1996 Feb;84(2):340-7. — View Citation

Tugrul S, Degirmenci N, Eren SB, Dogan R, Veyseller B, Ozturan O. Analgesic effect of magnesium in post-tonsillectomy patients: a prospective randomised clinical trial. Eur Arch Otorhinolaryngol. 2015 Sep;272(9):2483-7. doi: 10.1007/s00405-014-3219-8. Epub 2014 Aug 6. — View Citation

Ulugol A, Aslantas A, Ipci Y, Tuncer A, Hakan Karadag C, Dokmeci I. Combined systemic administration of morphine and magnesium sulfate attenuates pain-related behavior in mononeuropathic rats. Brain Res. 2002 Jul 5;943(1):101-4. — View Citation

Yousef AA, Al-deeb AE. A double-blinded randomised controlled study of the value of sequential intravenous and oral magnesium therapy in patients with chronic low back pain with a neuropathic component. Anaesthesia. 2013 Mar;68(3):260-6. doi: 10.1111/anae.12107. Epub 2012 Dec 17. — View Citation

* Note: There are 47 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary The oxycodone dosage needed to achieve satisfactory analgesia Patient's satisfactory analgesia is defined as NRS =4 14 days No
Secondary Level of pain relief The level of pain relief is measured using Pain Relief Scale 2 days No
Secondary Time to satisfactory analgesia The time needed to achieve satisfactory analgesia (NRS=4) from 2 to 14 days No
Secondary Time to 50% reduction of pain The time needed to achieve a reduction of pain of 50% using Pain Relief Scale(PRS = 50%) from 2 to 14 days No
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