Vitamin D for Chronic Pain After Burns

Overseen By Matthew Mauck

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of North Carolina, Chapel Hill

Must not be taking: Vitamin D supplements

Disqualifiers: Pregnancy, Psychosis, Liver disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 1 day

40 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this pilot clinical trial is to learn whether vitamin D is able to prevent chronic pain following burn injury and to determine what biological mechanisms are engaged by Vitamin D following burn injury. The main question\[s\] it aims to answer are: * Is the clinical trial protocol feasible? * Is Vitamin D administration following burn injury safe? * How does vitamin D cause changes in the immune system in the aftermath of burn injury? Following informed consent, participants will be asked to: * Take 6 capsules by mouth one time following burn injury (Vitamin D or Placebo) * Provide a blood sample at baseline and 6 weeks following injury * Fill out surveys daily while in the hospital, weekly through 6 weeks, and at 3 months and 6 months. Researchers will compare Vitamin D and placebo groups to see if there are differences in adverse effects (side effects), chronic pain, and profiles of immune cells from collected blood samples.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are taking Vitamin D supplements in excess of 800 IU daily, you may not be eligible to participate.

What evidence supports the effectiveness of the drug Vitamin D2 (Ergocalciferol) for chronic pain after burns?

Research suggests that low levels of Vitamin D are linked to worse chronic pain outcomes, and supplementation may improve pain, sleep, and quality of life in chronic pain patients. Vitamin D is thought to help with pain by interacting with pain signaling pathways and immune cells, although more studies are needed to understand these effects fully. ^{1 2 3 4 5}

Is Vitamin D safe for use in humans, particularly for those with chronic pain after burns?

Vitamin D, including forms like ergocalciferol (Vitamin D2), is generally considered safe for humans. It is important for bone and muscle health, and deficiencies can lead to issues like muscle weakness and itching, which are common in burn patients. However, more research is needed to fully understand its safety and effects in adult burn patients. ^{2 6 7 8 9}

How does the drug Ergocalciferol differ from other treatments for chronic pain after burns?

Ergocalciferol (Vitamin D2) is unique because it addresses chronic pain potentially linked to vitamin D deficiency, which is not typically targeted by standard pain medications. Unlike traditional analgesics, it may help improve pain by correcting vitamin D levels, especially in individuals with compromised vitamin D status, which is common in burn patients. ^{1 2 8 10 11}

Research Team

Matthew C Mauck, MD PhD

Principal Investigator

University of North Carolina, Chapel Hill

Eligibility Criteria

Adults aged 18-70 with thermal burns covering less than 30% of their body, experiencing significant pain (≥7/10), and admitted for surgical burn wound management. Participants must be alert, speak English, willing to take study medication, have a smartphone, and not have severe kidney disease or certain other health conditions.

Inclusion Criteria

Able to speak and read English

I am mentally alert and aware of my surroundings.

My burn injury is caused by heat, not electricity or chemicals.

Exclusion Criteria

Prisoner status

You have high levels of phosphorus in your blood.

You have high levels of calcium in your blood.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants take 6 capsules by mouth one time following burn injury (Vitamin D or Placebo)

1 day

1 visit (in-person)

Monitoring

Participants provide a blood sample at baseline and 6 weeks following injury and fill out surveys daily while in the hospital, weekly through 6 weeks

6 weeks

Multiple visits (in-person and virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with surveys at 3 months and 6 months

6 months

2 visits (in-person)

Treatment Details

Interventions

• Ergocalciferol
• Placebo

Trial Overview This trial is testing if Vitamin D can prevent chronic pain after a burn injury by comparing the effects of Vitamin D capsules to placebo. It will also explore how Vitamin D affects immune system changes post-injury through blood samples and surveys up to six months.

Participant Groups

Group I: Vitamin D2 (Ergocalciferol) Active Control 1 Intervention

One time, oral dose of Vitamin D2 administered via 6 50,000 IU Ergocalciferol capsules. Capsules will be encapsulated and masked to be indistinguishable from placebo.

Group II: Placebo Placebo Group 1 Intervention

One time, oral dose of 6 placebo capsules filled with inert powder and encapsulated and masked to be indistinguishable from active comparator.

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

Approved in United States as Ergocalciferol for:

• Rickets
• Osteomalacia
• Hypoparathyroidism
• Vitamin D deficiency

Approved in European Union as Ergocalciferol for:

• Rickets
• Osteomalacia
• Hypoparathyroidism
• Vitamin D deficiency

Approved in Canada as Ergocalciferol for:

• Rickets
• Osteomalacia
• Hypoparathyroidism
• Vitamin D deficiency

Who Is Running the Clinical Trial?

University of North Carolina, Chapel Hill

Lead Sponsor

Trials

1,588

Recruited

4,364,000+

National Center for Complementary and Integrative Health (NCCIH)

Collaborator

Trials

886

Recruited

677,000+

Findings from Research

Chronic pain affects about 50 million adults in the U.S., and current pain medications are often ineffective for many, with around 20% of patients experiencing no relief.

Vitamin D may offer a promising alternative for managing chronic pain due to its potential analgesic effects, which could involve interactions with pain signaling pathways and immune responses, although more research is needed to fully understand these mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin D and Its Potential Interplay With Pain Signaling Pathways. Habib, AM., Nagi, K., Thillaiappan, NB., et al.[2021]

In a study of 77 burn survivors, it was found that Black Americans had significantly lower peritraumatic Vitamin D levels compared to White Americans, with 73% of Black participants being Vitamin D deficient versus 35% of White participants.

Lower peritraumatic Vitamin D levels were linked to worse chronic pain outcomes after burn injuries, suggesting that Vitamin D deficiency may contribute to racial disparities in pain experiences among burn survivors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peritraumatic Vitamin D Levels Predict Chronic Pain Severity and Contribute to Racial Differences in Pain Outcomes Following Major Thermal Burn Injury. Mauck, MC., Barton, CE., Tungate, A., et al.[2022]

A study involving 28 veterans with chronic pain and low vitamin D levels showed that standardized vitamin D supplementation significantly improved pain, sleep quality, and overall quality of life without any reported side effects.

Participants experienced notable improvements in pain scores, sleep latency, sleep duration, bodily pain, general health, vitality, and social functioning, indicating that vitamin D may play a beneficial role in managing chronic pain conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement of pain, sleep, and quality of life in chronic pain patients with vitamin D supplementation. Huang, W., Shah, S., Long, Q., et al.[2022]

A systematic review of 81 observational studies involving over 50,000 participants found that patients with arthritis, muscle pain, and chronic widespread pain had significantly lower levels of 25-hydroxyvitamin D (25(OH)D) compared to controls, indicating a potential link between low vitamin D levels and these pain conditions.

The study also revealed that the odds of vitamin D deficiency were higher in individuals with arthritis, muscle pain, and chronic widespread pain, suggesting that monitoring and addressing vitamin D levels could be important in managing these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The association between vitamin D concentration and pain: a systematic review and meta-analysis. Wu, Z., Malihi, Z., Stewart, AW., et al.[2023]

Chronic pain is common in developed countries, and individuals with chronic pain often have lower levels of vitamin D compared to those without pain, suggesting a potential link between vitamin D deficiency and chronic pain conditions.

The paper reviews scientific evidence supporting vitamin D supplementation as a possible independent treatment for chronic pain, and it offers recommendations for its use in clinical practice for patients suffering from chronic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there role for vitamin D in the treatment of chronic pain? Martin, KR., Reid, DM.[2023]

Vitamin D deficiency is common in pediatric burn patients, but there is a lack of formal studies on its prevalence and effects in adult burn populations, highlighting a gap in research.

Vitamin D deficiency can lead to symptoms like itching, muscle weakness, and neuropathy, which are also frequently experienced by burn patients, suggesting that further investigation is needed to understand the impact of vitamin D levels on recovery in adults with burn injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin D deficiency in burn patients. Schumann, AD., Paxton, RL., Solanki, NS., et al.[2018]

In a study of 69 pediatric burn patients with severe injuries (average burn area of 50.6% TBSA), 62.3% had low levels of vitamin D, indicating a significant prevalence of vitamin D insufficiency in this population.

The study found that larger burn areas and inhalation injuries were associated with lower vitamin D levels, and there was a notable increase in hyperparathyroidism among patients with very low vitamin D levels, highlighting the need for further investigation into vitamin D management in burn care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypovitaminosis D in acutely injured pediatric burn patients. Gottschlich, MM., Mayes, T., Khoury, J., et al.[2018]

In a cohort study of 24 adult burn patients, 75% were found to have vitamin D insufficiency and 17% had a deficiency at the time of admission, indicating a high prevalence of hypovitaminosis D in this population.

Supplementation with low doses of cholecalciferol (vitamin D3) did not significantly improve serum levels of 25(OH)-D over four weeks, suggesting that current nutritional guidelines may need to be reevaluated for burn patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of cholecalciferol recommended daily allowances on vitamin D status and fibroblast growth factor-23: an observational study in acute burn patients. Rousseau, AF., Damas, P., Ledoux, D., et al.[2021]

In a pilot study involving 15 adults with thermal burns, cholecalciferol (VD3) supplementation effectively corrected vitamin D deficiency, with levels increasing significantly after one year.

While the VD3 and calcium regimen improved muscle strength, particularly in the quadriceps, it did not lead to significant changes in bone health, highlighting ongoing concerns about bone density in burn patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of cholecalciferol supplementation and optimized calcium intakes on vitamin D status, muscle strength and bone health: a one-year pilot randomized controlled trial in adults with severe burns. Rousseau, AF., Foidart-Desalle, M., Ledoux, D., et al.[2015]

Five patients experienced unusual hyperesthetic pain linked to low vitamin D levels, which resolved within 5 to 7 days after receiving vitamin D supplementation (ergocalciferol).

The pain did not respond to typical analgesics or tricyclic antidepressants, suggesting a specific pain syndrome related to vitamin D deficiency that can significantly impact mobility and function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can vitamin D deficiency produce an unusual pain syndrome? Gloth, FM., Lindsay, JM., Zelesnick, LB., et al.[2022]

In a large trial involving 21,315 participants aged 60-84, vitamin D3 supplementation at a dose of 60,000 IU per month showed no significant effect on bodily pain, as measured by the Pain Impact Questionnaire over 5 years.

The study found that both the vitamin D and placebo groups had similar pain scores and prevalence of pain, indicating that vitamin D supplementation does not alleviate pain in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of vitamin D supplementation on pain: an analysis of data from the D-Health randomised controlled trial. Rahman, A., Waterhouse, M., Baxter, C., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Vitamin D and Its Potential Interplay With Pain Signaling Pathways. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Peritraumatic Vitamin D Levels Predict Chronic Pain Severity and Contribute to Racial Differences in Pain Outcomes Following Major Thermal Burn Injury. [2022]

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

Improvement of pain, sleep, and quality of life in chronic pain patients with vitamin D supplementation. [2022]

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

The association between vitamin D concentration and pain: a systematic review and meta-analysis. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Is there role for vitamin D in the treatment of chronic pain? [2023]

6. England pubmed.ncbi.nlm.nih.gov

Vitamin D deficiency in burn patients. [2018]

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

Hypovitaminosis D in acutely injured pediatric burn patients. [2018]

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

Effect of cholecalciferol recommended daily allowances on vitamin D status and fibroblast growth factor-23: an observational study in acute burn patients. [2021]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of cholecalciferol supplementation and optimized calcium intakes on vitamin D status, muscle strength and bone health: a one-year pilot randomized controlled trial in adults with severe burns. [2015]

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

Can vitamin D deficiency produce an unusual pain syndrome? [2022]

11. England pubmed.ncbi.nlm.nih.gov

The effect of vitamin D supplementation on pain: an analysis of data from the D-Health randomised controlled trial. [2023]