Dexamethasone for Rhabdomyolysis

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Children's National Research Institute

Must not be taking: Systemic steroids

Disqualifiers: Pregnancy, Uncontrolled illness, Allergy, others

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 5 days

50 Participants Needed

Trial Summary

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 systemic steroids.

What evidence supports the effectiveness of the drug dexamethasone for treating rhabdomyolysis?

Research on rats with Crush syndrome, which involves muscle damage similar to rhabdomyolysis, shows that dexamethasone improved clinical outcomes and had therapeutic effects. This suggests potential benefits of dexamethasone for rhabdomyolysis. ^{1 2 3 4 5}

Is Dexamethasone generally safe for humans?

Dexamethasone, like other corticosteroids, can have side effects such as increased appetite, weight gain, and mood changes. In some cases, it may cause muscle weakness or other complications, especially with long-term use. It's important to monitor these effects and discuss them with a healthcare provider. ^{6 7 8 9 10}

How does the drug dexamethasone differ from other treatments for rhabdomyolysis?

Dexamethasone is unique in its potential use for rhabdomyolysis because it has shown therapeutic effects in a model of Crush syndrome, which involves rhabdomyolysis, by improving clinical outcomes and altering pharmacokinetic parameters. Unlike standard treatments, dexamethasone may offer benefits through its anti-inflammatory properties and effects on muscle tissue. ^{2 5 11 12 13}

What is the purpose of this trial?

There is a significant unmet need for optimized treatment in rhabdomyolysis. There are few prospective interventional studies on treatment for rhabdomyolysis, a condition which affects diverse and underrepresented populations at a higher rate. While steroids are often used off-label, a systematic study has not yet been initiated, and steroids have not been yet considered in as a consideration to standard care guidelines. The hypothesis is that patients who receive dexamethasone in addition to standard care versus placebo and standard care will have improvement in pain, length of hospital stay, and decrease in kidney complications.

Eligibility Criteria

This trial is for children with rhabdomyolysis, a muscle breakdown condition. It's open to those who meet certain health criteria but details on specific inclusions or exclusions aren't provided.

Inclusion Criteria

Ability of parents/patients to understand and the willingness to sign a written informed consent document

I am 12 or older and willing to sign a consent form.

I have been diagnosed with rhabdomyolysis with a creatine kinase level over 5000, without any injury.

Exclusion Criteria

Allergy to fluconazole, clotrimazole or nystatin

Inability to comply with study instructions

Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dexamethasone or placebo for 5 days in addition to standard care

5 days

Daily visits for oral dosing

Follow-up

Participants are monitored for safety and effectiveness after treatment, including pain assessment and chart review

14 days

Surveys before and after treatment

Extended Follow-up

Participants are monitored for long-term outcomes such as length of hospital stay and renal complications

Up to 1 year

Treatment Details

Interventions

• Dexamethasone

Trial Overview The study tests if adding dexamethasone (a steroid) to standard treatment helps reduce pain, shorten hospital stays, and prevent kidney problems better than the usual care plus a placebo.

Participant Groups

Group I: Dexamethasone group Active Control 1 Intervention

Dexamethasone five days with 0.6 mg/ kg dose per day max 16 mg dose. Standard care will also be provided.

Group II: Placebo group Placebo Group 1 Intervention

Placebo for five days with one dose per day placebo oral dosing. Standard care will also be provided.

Who Is Running the Clinical Trial?

Children's National Research Institute

Lead Sponsor

Trials

227

Recruited

258,000+

Findings from Research

Long-term corticosteroid treatment (over 3 years) in patients with Duchenne muscular dystrophy provides significant benefits, including prolonging ambulation by 2 to 5 years and improving overall neuromuscular function without major side effects.

Corticosteroids also reduce the need for spinal stabilization surgery, enhance cardiopulmonary function, delay the requirement for noninvasive ventilation, and improve both survival rates and quality of life for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Change in natural history of Duchenne muscular dystrophy with long-term corticosteroid treatment: implications for management. Moxley, RT., Pandya, S., Ciafaloni, E., et al.[2022]

Deflazacort treatment in boys with Duchenne muscular dystrophy (DMD) significantly delayed the loss of walking ability and improved pulmonary function compared to untreated boys, with treated boys maintaining better functional vital capacity at 15 years (88% vs. 39%).

While deflazacort was associated with the development of asymptomatic cataracts in 10 out of 30 boys, other side effects like hypertension and infections were not more common than in untreated boys, indicating a relatively favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deflazacort treatment of Duchenne muscular dystrophy. Biggar, WD., Gingras, M., Fehlings, DL., et al.[2014]

Deflazacort, approved for Duchenne muscular dystrophy (DMD) in 2017, shows similar or slower rates of functional decline compared to prednisone/prednisolone, based on evidence from various clinical studies.

While deflazacort has a better safety profile regarding weight gain and behavioral side effects, it may have more negative impacts on bone health, growth, and cataract development compared to prednisone/prednisolone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing Deflazacort and Prednisone in Duchenne Muscular Dystrophy. Biggar, WD., Skalsky, A., McDonald, CM.[2022]

In a double-blind trial involving 28 patients with Duchenne muscular dystrophy, Deflazacort (DF) showed statistically significant improvements in muscle strength and function compared to a placebo, indicating its efficacy as a treatment option.

While some mild side effects were observed, such as increased appetite and a cushingoid appearance in a few patients, no one had to stop taking the medication, suggesting that DF may have a better safety profile than traditional steroids like prednisone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Steroids in Duchenne muscular dystrophy--deflazacort trial. Mesa, LE., Dubrovsky, AL., Corderi, J., et al.[2019]

References

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

Effects of prednisolone on skeletal muscle contractility in mdx mice. [2021]

2. Japan pubmed.ncbi.nlm.nih.gov

[Pharmacokinetics characteristics of dexamethasone in Crush syndrome model rats]. [2015]

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

Change in natural history of Duchenne muscular dystrophy with long-term corticosteroid treatment: implications for management. [2022]

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

Novel approaches to corticosteroid treatment in Duchenne muscular dystrophy. [2022]

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

Deflazacort but not prednisone improves both muscle repair and fiber growth in diaphragm and limb muscle in vivo in the mdx dystrophic mouse. [2019]

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

Deflazacort treatment of Duchenne muscular dystrophy. [2014]

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

Acute myopathy in severe acute asthma treated with intravenously administered corticosteroids. [2004]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Comparing Deflazacort and Prednisone in Duchenne Muscular Dystrophy. [2022]

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

Glucocorticoids in Myositis: Initiation, Tapering, and Discontinuation. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Steroids in Duchenne muscular dystrophy--deflazacort trial. [2019]

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

Effects of the simultaneous administration of diethylstilbestrol and prednisolone on serum enzymes in Duchenne's muscular dystrophy. [2013]

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

Mineralocorticoid receptor antagonists and glucocorticoids differentially affect skeletal muscle inflammation and pathology in muscular dystrophy. [2023]

13. England pubmed.ncbi.nlm.nih.gov

Calcium influx inhibition by steroids and analogs in C2C12 skeletal muscle cells. [2016]