Prednisone for Complex Regional Pain Syndrome

Overseen By Alice (Wei Ting) Wang, MSc, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of British Columbia

Must not be taking: Glucocorticoids

Disqualifiers: Diabetes, Pregnancy, Infections, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 2 weeks

40 Participants Needed

Trial Summary

What is the purpose of this trial?

Wrist fractures are the most prevalent adult fracture. Complex regional pain syndrome (CRPS) is a common complication that can occur, leading to permanent disability and is costly to the patient and healthcare system. In addition, amidst the opioid epidemic, the risk of increased opioid use in patients with CRPS prompts the need to find viable treatment strategies. This study aims to evaluate an anti-inflammatory medication, prednisone, in the early treatment of CRPS. Patients with wrist fractures who undergo surgical treatment will be randomized to receiving placebo vs prednisone for 2 weeks. Clinical assessments in the follow up period will be compared.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are already taking a glucocorticoid medication like prednisone.

What data supports the effectiveness of the drug Prednisone for treating Complex Regional Pain Syndrome?

Research shows that corticosteroid therapy, which includes drugs like Prednisone, has shown favorable results in treating Complex Regional Pain Syndrome (CRPS), with studies indicating significant improvement in pain and symptoms when used in a structured treatment plan. ^{1 2 3 4 5}

Is prednisone safe for treating complex regional pain syndrome?

In a study comparing high-dose and low-dose oral steroid regimens for complex regional pain syndrome, no treatment-emergent adverse events like high blood pressure, blood sugar issues, or stomach problems were reported. ^{1 3 6 7 8}

How is the drug prednisone unique in treating complex regional pain syndrome?

Prednisone is a corticosteroid that helps reduce inflammation and is used to treat complex regional pain syndrome (CRPS) by potentially providing significant pain relief and improving symptoms when other treatments have failed. It is taken orally and has shown effectiveness in clinical studies, making it a promising option for CRPS, which lacks a standard treatment. ^{1 2 3 9 10}

Research Team

David Stockton, MD, MASc, FRCSC

Principal Investigator

University of British Columbia

Eligibility Criteria

This trial is for adults aged 19 or older who have had a wrist fracture treated with surgery. Participants must be female, have pain scores of at least 5/10 post-injury, show signs of CRPS according to the Budapest Criteria, and not be depressed as indicated by a CES-D score of 16 or higher.

Inclusion Criteria

I am 19 years old or older.

I have a confirmed single closed wrist fracture.

My depression score is 16 or higher.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either prednisone or placebo for 2 weeks starting on the day of surgery

2 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at 2 weeks, 6 weeks, 3 months, and 6 months

6 months

4 visits (in-person)

Treatment Details

Interventions

• Prednisone

Trial Overview The study tests if prednisone, an anti-inflammatory drug, can prevent complex regional pain syndrome (CRPS) after wrist fractures. Patients are randomly chosen to receive either prednisone or a placebo for two weeks following surgical repair.

Participant Groups

Group I: Prednisone Experimental Treatment 1 Intervention

40 mg PO once daily for 14 days starting day of surgery

Group II: Placebo Placebo Group 1 Intervention

placebo tablet PO once daily for 14 days starting day of surgery

Prednisone is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Prednisone for:

• Allergic reactions
• Asthma
• Blood disorders
• Cancer
• Eye problems
• Immune system disorders
• Inflammatory conditions
• Multiple sclerosis
• Organ transplantation
• Rheumatoid arthritis
• Skin conditions

Approved in European Union as Prednisone for:

• Allergic reactions
• Asthma
• Blood disorders
• Cancer
• Eye problems
• Immune system disorders
• Inflammatory conditions
• Multiple sclerosis
• Organ transplantation
• Rheumatoid arthritis
• Skin conditions

Approved in Canada as Prednisone for:

• Allergic reactions
• Asthma
• Blood disorders
• Cancer
• Eye problems
• Immune system disorders
• Inflammatory conditions
• Multiple sclerosis
• Organ transplantation
• Rheumatoid arthritis
• Skin conditions

Who Is Running the Clinical Trial?

University of British Columbia

Lead Sponsor

Trials

1,506

Recruited

2,528,000+

Canadian Orthopaedic Foundation

Collaborator

Trials

15

Recruited

1,900+

Findings from Research

In a study of 39 patients with complex regional pain syndrome (CRPS), nearly half (48.7%) experienced complete pain resolution after a 28-day taper of prednisone, indicating its effectiveness in managing CRPS symptoms.

All patients showed significant reductions in symptoms after treatment, but nearly half still had range of motion deficits, suggesting that while prednisone is effective for pain, additional therapies may be needed to fully restore mobility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prednisone for Acute Complex Regional Pain Syndrome: A Retrospective Cohort Study. Jamroz, A., Berger, M., Winston, P.[2020]

Complex regional pain syndrome type 1 (CRPS-1) is often underdiagnosed and can lead to significant disability, with diagnosis relying on clinical criteria rather than a gold standard test.

In a case study of a 47-year-old male with severe neuropathic pain, treatment with methylprednisolone (a corticosteroid) resulted in significant improvement over 15 days, highlighting the potential efficacy of corticosteroids in managing CRPS-1.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Complex regional pain syndrome type 1. An elusive diagnosis]. Forden Jones, RM., De Marco, RJ., Dombrowski, FA., et al.[2016]

A review of 11 studies indicates that oral prednisolone is effective in controlling symptoms of complex regional pain syndrome (CRPS), with dosages as low as 30 mg/day showing positive results.

The treatment duration varied, with effectiveness noted in both short-term (1-2 weeks) and longer-term (1-3 months) use, and only a small percentage (0%-30%) of patients experienced minor side effects, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of prednisolone in complex regional pain syndrome treatment: A systematic narrative review. Kwak, SG., Choo, YJ., Chang, MC.[2022]

In a study involving 31 patients with Complex Regional Pain Syndrome (CRPS) lasting over 3 months, oral steroids (prednisolone) did not show a significant overall reduction in pain intensity after treatment, suggesting limited efficacy for this condition.

Despite the lack of significant results, a few patients experienced notable pain relief, indicating that there may be specific subgroups of CRPS patients who could potentially benefit from steroid treatment, warranting further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Treatment of Longstanding Complex Regional Pain Syndrome with Oral Steroids. Barbalinardo, S., Loer, SA., Goebel, A., et al.[2017]

In a study of 21 hemiplegic stroke patients with complex regional pain syndrome (CRPS) type I, both intravenous pamidronate and oral prednisolone were found to significantly reduce pain and hand swelling over a four-week follow-up period, indicating their effectiveness in managing CRPS.

Pamidronate was shown to be safe and well-tolerated, with no significant adverse effects reported, suggesting it could be a viable alternative to steroids for pain control in CRPS, although the small sample size means further research is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pamidronate effect compared with a steroid on complex regional pain syndrome type I: Pilot randomised trial. Eun Young, H., Hyeyun, K., Sang Hee, I.[2022]

In a study of 50 patients with complex regional pain syndrome type I (CRPS-I), prednisolone 20 mg was found to be as effective as 40 mg in reducing pain, with all patients achieving over 50% reduction in pain scores after one month.

The lower dose of prednisolone (20 mg) was safer for diabetic patients, requiring fewer adjustments to their antidiabetic medications compared to the higher dose (40 mg).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prednisolone 20 mg vs 40 mg in complex regional pain syndrome type I: A randomized controlled trial. Kalita, J., Pandey, PC., Shukla, R., et al.[2023]

In a study of 34 patients with complex regional pain syndrome type I (CRPS I), both high-dose and low-dose oral steroid regimens showed similar efficacy in reducing pain severity and improving clinical scores over a 2-week period.

No significant adverse events were reported, indicating that low-dose steroids may be a safer alternative to high-dose regimens without compromising treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Oral Prednisolone and a 3-Phase Bone Scintigraphy in Patients with Complex Regional Pain Syndrome Type I. Park, S., Kim, HJ., Kim, DK., et al.[2020]

In a study of 31 patients with complex regional pain syndrome (CRPS), low-dose systemic corticosteroid therapy showed significant long-term efficacy in reducing pain and improving function, with results remaining positive even one year after treatment (P<0.001).

The corticosteroid therapy was associated with a low risk of side effects, making it a safe option for managing CRPS symptoms, and an arbitrary clinical severity scale developed for CRPS showed significant improvement over the follow-up period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term functional outcome measures in corticosteroid-treated complex regional pain syndrome. Bianchi, C., Rossi, S., Turi, S., et al.[2009]

In a study of 23 patients with reflex dystrophy syndrome, those treated with oral prednisone showed significant improvement, with all 13 patients experiencing over 75% clinical improvement within 12 weeks.

In contrast, only 2 out of 10 patients receiving a placebo reported any improvement, suggesting that prednisone is a more effective treatment for this condition, although its exact mechanism of action remains unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The reflex dystrophy syndrome response to treatment with systemic corticosteroids. Christensen, K., Jensen, EM., Noer, I.[2013]

In a study involving 58 post-stroke patients with complex regional pain syndrome-1 (CRPS-I), long-term low-dose prednisolone (10 mg daily) was found to be safe and effective, with 96.5% of patients initially responding to a higher dose.

Patients who continued on prednisolone showed further improvement in CRPS scores, while half of those who stopped treatment experienced a deterioration in their condition, highlighting the importance of ongoing treatment for managing symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Prednisolone in Post-stroke Complex Regional Pain Syndrome. Kalita, J., Misra, U., Kumar, A., et al.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Prednisone for Acute Complex Regional Pain Syndrome: A Retrospective Cohort Study. [2020]

2. Argentina pubmed.ncbi.nlm.nih.gov

[Complex regional pain syndrome type 1. An elusive diagnosis]. [2016]

3. United States pubmed.ncbi.nlm.nih.gov

Effectiveness of prednisolone in complex regional pain syndrome treatment: A systematic narrative review. [2022]

4. England pubmed.ncbi.nlm.nih.gov

The Treatment of Longstanding Complex Regional Pain Syndrome with Oral Steroids. [2017]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Pamidronate effect compared with a steroid on complex regional pain syndrome type I: Pilot randomised trial. [2022]

6. Scotland pubmed.ncbi.nlm.nih.gov

Prednisolone 20 mg vs 40 mg in complex regional pain syndrome type I: A randomized controlled trial. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Use of Oral Prednisolone and a 3-Phase Bone Scintigraphy in Patients with Complex Regional Pain Syndrome Type I. [2020]

8. Italy pubmed.ncbi.nlm.nih.gov

Long-term functional outcome measures in corticosteroid-treated complex regional pain syndrome. [2009]

9. Sweden pubmed.ncbi.nlm.nih.gov

The reflex dystrophy syndrome response to treatment with systemic corticosteroids. [2013]

10. United States pubmed.ncbi.nlm.nih.gov

Long-term Prednisolone in Post-stroke Complex Regional Pain Syndrome. [2018]