Peripheral Arterial DiseaseNCT02455726
Magnesium Oral Supplementation to Reduce Pain Inpatients With Severe Peripheral Arterial Occlusive Disease
A study testing Magnesium oxide, Fructose and Oxycodone in people with Peripheral Arterial Disease, run by Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Peripheral Arterial Disease
- What is being tested?
- Magnesium oxide, Fructose and Oxycodone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- No sites listed yet
- Study dates
- Sep 2015to Dec 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
No sites are listed yet.
Monica A Venturini, Doctor contact
Nicola Latronico, Professor contact
About this study
Official title: Magnesium Oral Supplementation to Reduce Pain in Patients With Severe Peripheral Arterial Occlusive Disease: The MAG-PAPER Randomized Clinical Trial
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.
Read the detailed 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.
- Conditions
- Peripheral Arterial Disease
- Being tested
- Magnesium oxide, Fructose, Oxycodone, Pregabalin
- Keywords
- Peripheral Arterial Disease, Magnesium Oxide, Pain
- Medical subject headings
- Peripheral Arterial Disease, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Magnesium oxideDietary supplement
Oral magnesium oxide 300 mg twice a day
FructoseDietary supplement
Oral fructose 10 g twice a day
OxycodoneDrug
Also called Oxycontin, Mundipharma Pharmaceutic
Oxycodone hydrochloride 5 mg at 8 am
PregabalinDrug
Also called Lyrica, Pfizer Italia
Pregabalin 25 mg at 8 pm
| Study group | Role | What they receive |
|---|---|---|
| Mg-group | Experimental | Standard therapy plus magnesium oxide.
* Standard therapy: oxycodone 5 mg and pregabalin 25 mg per day for two weeks. Starting by day 2, the opioid dose will be titrated every 48 hours in order to reach the maximum therapeutic goal and to minimize side effects.
* A rescue dose: paracetamol 1g (maximum dose 3 g per day). Receives: Dietary Supplement: Magnesium oxide; Drug: Oxycodone; Drug: Pregabalin |
| C-group | Placebo comparator | Standard therapy plus fructose.
* Standard therapy: oxycodone 5 mg and pregabalin 25 mg per day for two weeks. Starting by day 2, the opioid dose will be titrated every 48 hours in order to reach the maximum therapeutic goal and to minimize side effects.
* A rescue dose: paracetamol 1g (maximum dose 3 g per day). Receives: Dietary Supplement: Fructose; Drug: Oxycodone; Drug: Pregabalin |
What is being measured
The primary outcome is the main question the study is designed to answer.
The oxycodone dosage needed to achieve satisfactory analgesia
Patient's satisfactory analgesia is defined as NRS ≤4
Measured: 14 days
Secondary outcomes (3)
Level of pain relief
The level of pain relief is measured using Pain Relief Scale
Measured: 2 days
Time to satisfactory analgesia
The time needed to achieve satisfactory analgesia (NRS≤4)
Measured: from 2 to 14 days
Time to 50% reduction of pain
The time needed to achieve a reduction of pain of 50% using Pain Relief Scale(PRS = 50%)
Measured: from 2 to 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2015 (estimated)
- Study startSep 2015
- Primary completionDec 2017 (estimated)
- Study completionDec 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (48)Papers the sponsor has linked to this study.
- Other trials for Peripheral Arterial DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Monica Aida Venturini, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
- Investigators
- Monica A Venturini, Doctor, Principal investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02455726
- Sponsor's protocol ID
- 1601 gluta-aos
- Status last verified
- May 2015
- First submitted
- 23 Apr 2015
- Last updated
- 28 May 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
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. No abstract available.
PubMed 23700072Fowkes 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.
PubMed 23915883Iseri LT, French JH. Magnesium: nature's physiologic calcium blocker. Am Heart J. 1984 Jul;108(1):188-93. doi: 10.1016/0002-8703(84)90572-6. No abstract available.
PubMed 6375330Kew JN, Kemp JA. Ionotropic and metabotropic glutamate receptor structure and pharmacology. Psychopharmacology (Berl). 2005 Apr;179(1):4-29. doi: 10.1007/s00213-005-2200-z. Epub 2005 Feb 25.
PubMed 15731895Recio-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
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. doi: 10.1016/s0885-3924(00)00213-x.
PubMed 11068158Hewitt DJ. The use of NMDA-receptor antagonists in the treatment of chronic pain. Clin J Pain. 2000 Jun;16(2 Suppl):S73-9. doi: 10.1097/00002508-200006001-00013.
PubMed 10870744De 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. doi: 10.1016/j.bpa.2006.12.006.
PubMed 17489221Petrenko 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):1108-1116. doi: 10.1213/01.ANE.0000081061.12235.55.
PubMed 14500166Nechifor M. Magnesium involvement in pain. Magnes Res. 2011 Dec;24(4):220-2. doi: 10.1684/mrh.2011.0296. No abstract available.
PubMed 22061718Hasanein 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. doi: 10.1016/j.diabres.2005.12.004. Epub 2006 Jan 18.
PubMed 16417942Rondon 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.
PubMed 20837644Begon 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. doi: 10.1097/00000542-200203000-00019.
PubMed 11873038Bujalska M, Makulska-Nowak H, Gumulka SW. Magnesium ions and opioid agonists in vincristine-induced neuropathy. Pharmacol Rep. 2009 Nov-Dec;61(6):1096-104. doi: 10.1016/s1734-1140(09)70172-0.
PubMed 20081245Ulugol 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. doi: 10.1016/s0006-8993(02)02618-5.
PubMed 12088843
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Magnesium Oral Supplementation to Reduce Pain in Patients With Severe Peripheral Arterial Occlusive Disease: The MAG-PAPER Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT02455726
- Acronym / sponsor ID
- 1601 gluta-aos
- Conditions
- Peripheral Arterial Disease
- Keywords
- Peripheral Arterial Disease, Magnesium Oxide, Pain
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Azienda Socio Sanitaria Territoriale degli Spedali Civili di BresciaUniversity, hospital or other
- Study start
- Sep 2015
- Primary completion
- Dec 2017 (estimated)
- Study completion
- Dec 2017 (estimated)
- First posted
- 28 May 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mg-group | Experimental | Dietary Supplement: Magnesium oxide, Drug: Oxycodone, Drug: PregabalinStandard therapy plus magnesium oxide. * Standard therapy: oxycodone 5 mg and pregabalin 25 mg per day for two weeks. Starting by day 2, the opioid dose will be titrated every 48 hours in order to reach the maximum therapeutic goal and to minimize side effects. * A rescue dose: paracetamol 1g (maximum dose 3 g per day). |
| C-group | Placebo comparator | Dietary Supplement: Fructose, Drug: Oxycodone, Drug: PregabalinStandard therapy plus fructose. * Standard therapy: oxycodone 5 mg and pregabalin 25 mg per day for two weeks. Starting by day 2, the opioid dose will be titrated every 48 hours in order to reach the maximum therapeutic goal and to minimize side effects. * A rescue dose: paracetamol 1g (maximum dose 3 g per day). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (6 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Magnesium oxideOral magnesium oxide 300 mg twice a day | Dietary supplement | Mg-group |
| FructoseOral fructose 10 g twice a day | Dietary supplement | C-group |
| OxycodoneAlso: Oxycontin, Mundipharma PharmaceuticOxycodone hydrochloride 5 mg at 8 am | Drug | C-group, Mg-group |
| PregabalinAlso: Lyrica, Pfizer ItaliaPregabalin 25 mg at 8 pm | Drug | C-group, Mg-group |
Primary outcome
The oxycodone dosage needed to achieve satisfactory analgesia
Time frame: 14 days
Patient's satisfactory analgesia is defined as NRS ≤4
3 secondary outcomes
Level of pain relief
Time frame: 2 days
Time to satisfactory analgesia
Time frame: from 2 to 14 days
Time to 50% reduction of pain
Time frame: from 2 to 14 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2015.
- Background: PubMed 23700072Dowell 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. No abstract available.
- Background: PubMed 23915883Fowkes 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.
- Background: PubMed 6375330Iseri LT, French JH. Magnesium: nature's physiologic calcium blocker. Am Heart J. 1984 Jul;108(1):188-93. doi: 10.1016/0002-8703(84)90572-6. No abstract available.
- Background: PubMed 15731895Kew JN, Kemp JA. Ionotropic and metabotropic glutamate receptor structure and pharmacology. Psychopharmacology (Berl). 2005 Apr;179(1):4-29. doi: 10.1007/s00213-005-2200-z. Epub 2005 Feb 25.
- BackgroundRecio-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
- Background: PubMed 11068158Fisher 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. doi: 10.1016/s0885-3924(00)00213-x.
- Background: PubMed 10870744Hewitt DJ. The use of NMDA-receptor antagonists in the treatment of chronic pain. Clin J Pain. 2000 Jun;16(2 Suppl):S73-9. doi: 10.1097/00002508-200006001-00013.
- Background: PubMed 17489221De 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. doi: 10.1016/j.bpa.2006.12.006.
- Background: PubMed 14500166Petrenko 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):1108-1116. doi: 10.1213/01.ANE.0000081061.12235.55.
- Background: PubMed 22061718Nechifor M. Magnesium involvement in pain. Magnes Res. 2011 Dec;24(4):220-2. doi: 10.1684/mrh.2011.0296. No abstract available.
- Background: PubMed 16417942Hasanein 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. doi: 10.1016/j.diabres.2005.12.004. Epub 2006 Jan 18.
- Background: PubMed 20837644Rondon 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Monica A Venturini, Doctor contact
Nicola Latronico, Professor contact
Monica A Venturini, Doctor principal investigator
Questions about this trial
What is this clinical trial studying?
A study testing Magnesium oxide, Fructose and Oxycodone in people with Peripheral Arterial Disease, run by Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 May 2015. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Monica A Venturini, Doctor (monica.venturini@spedalicivili.brescia.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The oxycodone dosage needed to achieve satisfactory analgesia (time frame: 14 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02455726, which also lists 48 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2015.