Capsaicin + Oxygen + Cold Stimuli for Headache

(PBS Trial)

Overseen By Mark Burish, MD PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: The University of Texas Health Science Center, Houston

Disqualifiers: Cardiovascular diseases, Brain tumors, Epilepsy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how different treatments can manage headaches by studying their underlying biological markers. Researchers will use capsaicin (from hot peppers) to trigger bodily responses, oxygen to assess its effect on eye watering and headaches, and ice water to induce short headaches similar to brain freeze. Individuals with ongoing headaches, such as migraines or cluster headaches, or those with back pain, might find this study relevant. Participants should have no history of debilitating headaches or back pain in the past three months and must be free of major cardiovascular or neurovascular issues. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this novel approach.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it is best to discuss your specific situation with the trial coordinators.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that capsaicin, the active ingredient in hot chili peppers, is generally safe as a treatment. Taken orally, it can accidentally irritate the eyes, skin, and moist linings inside the body. Applied to the skin, it may cause a tingling or burning sensation. Using capsaicin inside the nose can safely improve symptoms, though some people might experience a temporary burning sensation.

High flow oxygen therapy is safe and treats severe headaches called cluster headaches. Low flow oxygen is also safe and helps relieve pain in headache disorders.

Cold water therapy, such as using ice water to trigger headaches, is generally safe but can cause short, intense headaches.

This study is a Phase 1 trial, marking the first time the treatment is tested for safety in humans. Researchers closely monitor participants for any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these headache treatments because they explore a unique combination of capsaicin and oxygen therapy, along with cold stimuli. Unlike standard headache treatments, which often rely on medications like NSAIDs or triptans, these investigational approaches use capsaicin, a compound derived from chili peppers known for its pain-relieving properties, and oxygen therapy to potentially provide faster relief. The study tests various delivery methods, including oral, topical, and intranasal capsaicin, combined with different oxygen flows and cold water irrigation. This innovative method aims to target headache pain through multiple sensory pathways, offering the potential for rapid and effective relief.

What evidence suggests that this trial's treatments could be effective for headaches?

Research shows that capsaicin, the main component in chili peppers, may help treat headaches. In this trial, participants may receive capsaicin orally, topically, or intranasally. Studies have found that oral capsaicin can provide lasting pain relief for some people, while topical application significantly reduces migraine pain for many. Intranasal capsaicin quickly relieves headache pain for most patients.

Cold water irrigation, another treatment arm in this trial, creates a "brain freeze" sensation and can instantly reduce migraine pain, though the long-term effects remain unclear. Participants may also receive high-flow oxygen therapy, which has been effective, especially for cluster headaches, with noticeable symptom relief shortly after treatment. Low-flow oxygen, another option in this trial, also helps ease head pain in primary headache disorders like cluster headaches. ^{6 7 8 9 10}

Who Is on the Research Team?

Mark Burish MD PhD

Principal Investigator

The University of Texas Health Science Center, Houston

Are You a Good Fit for This Trial?

This trial is for adults who have been diagnosed with various headache disorders, including migraines and cluster headaches. They must be able to share medical records and not have a history of serious cardiovascular or neurovascular diseases, brain tumors, epilepsy, or be pregnant. Smokers and those with a life expectancy less than 1 year are excluded.

Inclusion Criteria

I have been diagnosed with a type of primary headache, such as migraine or tension headache.

I have been diagnosed with lumbar radiculopathy by a pain specialist.

The individual is able to provide authorization to share their prior medical records and imaging with healthcare providers.

Exclusion Criteria

You smoke or use tobacco or nicotine every day.

Active pregnancy or lactation

Active drug/alcohol use or dependence that would interfere with adherence to study requirements

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Capsaicin Application

Participants receive capsaicin in various forms (cream, nasal, oral) to trigger biomarker release

1 day per intervention

Multiple visits for different interventions

Oxygen and Eye Watering

Participants receive oxygen gas to assess its effect on eye watering triggered by capsaicin

1 day per intervention

Multiple visits for different interventions

Ice Water Application

Participants undergo ice water application to trigger headaches and assess biomarker release

1 day per intervention

Multiple visits for different interventions

Follow-up

Participants are monitored for safety and effectiveness after interventions

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Brain Freeze
• Cold Water Irrigation
• High Flow Oxygen
• Intranasal Capsaicin
• Low Flow Oxygen
• Medical Air
• Oral Capsaicin
• Topical Capsaicin

Trial Overview The study tests if capsaicin (from chili peppers) affects biomarkers in headache sufferers differently from controls when applied as cream, ingested, or used intranasally. It also examines if oxygen gas can reduce eye watering triggered by capsaicin and if ice water can simulate headaches to understand underlying mechanisms.

How Is the Trial Designed?

Group I: Topical capsaicin and Low Flow Oxygen Experimental Treatment 2 Interventions

Group II: Topical capsaicin and High Flow Oxygen Experimental Treatment 2 Interventions

Group III: Topical capsaicin Experimental Treatment 1 Intervention

Group IV: Oral capsaicin and High Flow Oxygen Experimental Treatment 2 Interventions

Group V: Oral capsaicin Experimental Treatment 1 Intervention

Group VI: Oral Capsaicin and Low Flow Oxygen Experimental Treatment 2 Interventions

Group VII: Intranasal capsaicin and Low Flow Oxygen Experimental Treatment 2 Interventions

Group VIII: Intranasal capsaicin and High Flow Oxygen Experimental Treatment 2 Interventions

Group IX: Intranasal capsaicin Experimental Treatment 1 Intervention

Group X: Cold water irrigation and Low Flow Oxygen Experimental Treatment 2 Interventions

Group XI: Cold water irrigation and High Flow Oxygen Experimental Treatment 2 Interventions

Group XII: Cold water irrigation Experimental Treatment 1 Intervention

Group XIII: Intranasal capsaicin and Medical Air Placebo Group 2 Interventions

Group XIV: Topical capsaicin and Medical Air Placebo Group 2 Interventions

Group XV: Cold water irrigation and Medical Air Placebo Group 2 Interventions

Group XVI: Oral capsaicin and Medical Air Placebo Group 2 Interventions

Who Is Running the Clinical Trial?

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

University of California, San Francisco

Collaborator

Trials

2,636

Recruited

19,080,000+

Published Research Related to This Trial

In a study involving 57 cluster headache patients, the use of demand valve oxygen (DVO) showed a significant preference among patients and was more effective in achieving pain relief during the first attack compared to other mask types.

While the primary endpoint of pain relief at 15 minutes was not statistically significant, both DVO and O2ptimask reduced the need for rescue medication, suggesting they are effective options for acute treatment of cluster headaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxygen therapy for cluster headache. A mask comparison trial. A single-blinded, placebo-controlled, crossover study. Petersen, AS., Barloese, MC., Lund, NL., et al.[2017]

Inhaled normobaric oxygen is an effective abortive treatment for cluster headaches, with its efficacy recognized for over 50 years, yet it has been under-discussed in the literature.

The article draws on data from the largest study of cluster headache patients, the United States Cluster Headache Survey, highlighting the importance of inhaled oxygen in a broad, real-world population rather than just clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhaled Oxygen for Cluster Headache: Efficacy, Mechanism of Action, Utilization, and Economics. Rozen, TD.[2021]

In a study of 16 patients with cluster headaches, hyperbaric oxygen (HBO) treatment did not show a significant advantage over a placebo treatment in reducing headache severity or frequency, indicating that the hyperbaric condition itself may not be an effective intervention for chronic cluster headaches.

Despite the lack of difference in headache index between HBO and sham treatments, a notable 83% of episodic cluster headache patients and 25% of chronic patients experienced at least a 50% reduction in headache severity, suggesting a strong placebo effect or individual variability in response to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperbaric oxygen treatment of active cluster headache: a double-blind placebo-controlled cross-over study. Nilsson Remahl, AI., Ansjön, R., Lind, F., et al.[2017]

In a study involving 14 patients with chronic cluster headache, hyperbaric oxygen (HBO2) treatment showed clinical effectiveness, while the placebo group showed no changes in headache frequency or medication use.

The HBO2 treatment appeared to influence serotonergic pathways, as indicated by changes in serotonin binding to mononuclear cells, suggesting a potential mechanism of action for alleviating cluster headache symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperbaric oxygen in chronic cluster headaches: influence on serotonergic pathways. Di Sabato, F., Rocco, M., Martelletti, P., et al.[2013]

Qutenza, a high-potency capsaicin patch, significantly reduces pain associated with postherpetic neuralgia (PHN), showing a 29.6% to 32% reduction in pain compared to a control patch, with effects lasting up to 12 weeks.

The most common side effects include application site erythema (63%) and pain (42%), and it must be administered by a physician, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capsaicin 8% topical patch (Qutenza)--a review of the evidence. Jones, VM., Moore, KA., Peterson, DM.[2013]

Oxygen therapy (OT) is an effective acute treatment for cluster headaches, with inhalation of 100% oxygen at flow rates of 6-12 L/min for 15-30 minutes being standard, although higher flow rates up to 15 L/min may provide even better relief.

While OT has shown efficacy in treating cluster headaches and some evidence in migraines, challenges in obtaining consistent results arise from varying inhalation protocols and small sample sizes in studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxygen Therapy in Cluster Headache, Migraine, and Other Headache Disorders. Mo, H., Chung, SJ., Rozen, TD., et al.[2022]

High-flow oxygen inhalation is an effective acute treatment for cluster headaches, showing advantages over other medications since its introduction in 1952.

The exact mechanism of action is not fully understood, but it is believed to be linked to the trigeminovascular system and neuroinflammation, making it a preferred option for patients who experience frequent attacks or cannot tolerate other drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of oxygen in cluster headache. Guo, XN., Lu, JJ., Ni, JQ., et al.[2021]

In a clinical trial involving 136 adult patients with moderate to severe primary headaches, the use of a non-rebreather mask (NRB) delivering oxygen at 15 l/min showed the most significant pain reduction at 30 minutes compared to other oxygen delivery methods.

However, the pain relief effect of the NRB method diminished by 60 minutes, indicating that while it may provide quick relief, it does not sustain significant pain reduction over a longer period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing the effects of 3 oxygen delivery methods plus intravenous ketorolac on primary headaches: A randomized clinical trial. Saeedi, M., Shahvaran, SM., Ramezani, M., et al.[2020]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35596276/

Cold intervention for relieving migraine symptoms Cold intervention is an effective regimen to reduce migraine pain instantly. The long-term effect of cold interventions on migraine is not demonstrated.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC1697736/

Cold Therapy in Migraine Patients: Open-label, Non- ... Fifteen out of twenty migraine patients and six out of seven tension headache patients experienced some reduction in headache severity. In another study, 9% of ...

3. thejournalofheadacheandpain.biomedcentral.com thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/1129-2377-16-5

Therapeutic effect of intranasal evaporative cooling in patients ... Intranasal evaporative cooling gave considerable benefit to patients with migraine, improving headache severity and migraine-associated symptoms.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1388245716301948

EP 89. Experimental provocation of “ice-cream headache” ... The ice water stimulus provoked HICS significantly more often than the ice cube stimulus. HICS provoked by ice water had a shorter latency, shorter duration, ...

5. journals.sagepub.com journals.sagepub.com/doi/full/10.1177/0333102416650704

Experimental provocation of 'ice-cream headache' by ice ... Ice water is more effective in triggering 'headache attributed to ingestion or inhalation of a cold stimulus' (HICS) than ice cubes. •. HICS ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/11442559/

Headache caused by drinking cold water is common and ... Headache caused by drinking cold water is common in women. The results indicate that active migraine facilitates the perception of forehead pain.

7. timesofindia.indiatimes.com timesofindia.indiatimes.com/life-style/health-fitness/health-news/5-serious-health-risks-of-pouring-cold-water-on-your-head/articleshow/123080129.cms

5 serious health risks of pouring cold water on your head Splashing cold water on the head can trigger serious health issues. It may cause cardiovascular stress, intense headaches, inner-ear imbalance, ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11872954/

The untapped potential of cold water therapy as part of a ... Cold water therapy presents a potential lifestyle strategy to enhancing physical and mental well-being, promoting healthy aging and extending the healthspan.

9. researchgate.net researchgate.net/publication/11897868_Headache_Caused_by_Drinking_Cold_Water_is_Common_and_Related_to_Active_Migraine

Headache Caused by Drinking Cold Water is Common and ... Headache caused by drinking cold water is common in women. The results indicate that active migraine facilitates the perception of forehead pain.

10. clinicaltrials.gov clinicaltrials.gov/study/NCT03511846

Study Details | NCT03511846 | Pain Biomarker Study Use of ice water to trigger headaches - brain freeze causes a very short-lived but intense headache that may cause similar biomarker release as other headache ...