Mind and Body Approaches for Migraine

Overseen By LeighAnn Chamberlin, MEd

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Children's Hospital Medical Center, Cincinnati

Must not be taking: Opioids, Antipsychotics, Benzodiazepines, others

Disqualifiers: Epilepsy, Neurological diseases, Psychiatric diseases, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

132 Participants Needed

Trial Summary

What is the purpose of this trial?

The overarching objective of this protocol is to identify and understand the neural and pain processing mechanisms by which youth with migraine improve in response to preventive treatment. The study design of this mechanistic investigation includes functional magnetic resonance imaging (fMRI), daily headache diaries, assessment of conditioned pain modulation via quantitative sensory testing, and validated psychometric assessments before and after the delivery of one of five treatments over an 8 week period \[cognitive behavioral therapy (CBT), biofeedback-assisted relaxation training (BART) and cognitive reappraisal (CR) training, amitriptyline, and placebo\]. We are examining both distinct and common pathways that may help explain the response to various preventive treatments, as well as potential predictors of outcome.

Do I have to stop taking my current medications for the trial?

Yes, you may need to stop certain medications. You cannot take prophylactic anti-migraine medication before the trial and must avoid starting any during the study. You also cannot use opioids, antipsychotics, antimanics, barbiturates, benzodiazepines, muscle relaxants, sedatives, tramadol, or nutraceuticals. Additionally, you must limit the use of NSAIDs to no more than 3 times per week and triptans to no more than 6 times per month.

Will I have to stop taking my current medications?

The trial requires that you do not take certain medications, such as NSAIDs more than 3 times a week, or migraine-specific medications like triptans more than 6 times a month. You also cannot be on any current migraine prevention medication or certain other medications like opioids, antipsychotics, or muscle relaxants during the study.

What data supports the idea that Mind and Body Approaches for Migraine is an effective treatment?

The available research shows that Mind and Body Approaches for Migraine, such as biofeedback-assisted relaxation training (BART) and cognitive-behavioral therapy (CBT), are effective treatments. One study found that patients using BART experienced more pain reduction and needed less medication compared to those who relaxed on their own. Another study showed that CBT led to a 68% reduction in headaches, which was more effective than biofeedback alone and much better than no treatment. Additionally, a study comparing CBT and the drug amitriptyline found that both treatments significantly improved headache symptoms, but CBT had slightly better outcomes. These findings suggest that Mind and Body Approaches can effectively reduce migraine symptoms. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment for migraines?

Research shows that biofeedback-assisted relaxation training (BART) and cognitive-behavioral therapy (CBT) can significantly reduce migraine headaches. BART has been shown to decrease pain and medication use, while CBT has been effective in reducing headache frequency and improving coping skills. ^{1 2 3 4 5}

What safety data exists for mind and body approaches for migraine treatment?

The safety data for mind and body approaches, including cognitive-behavioral therapy (CBT), biofeedback-assisted relaxation training (BART), and amitriptyline, indicate that these treatments are generally effective and well-tolerated. Studies show that CBT and BART can lead to significant improvements in headache activity and are often more accepted by patients compared to pharmacological treatments like amitriptyline. While both pharmacological and nonpharmacological treatments show clinical improvements, nonpharmacological treatments like relaxation and biofeedback may have longer-lasting effects without the need for additional treatment. However, these findings are preliminary, and further research is needed to confirm these results. ^{1 2 3 6 7}

Is the Mind and Body Approaches for Migraine treatment safe for humans?

Amitriptyline, a medication used in some migraine treatments, has been shown to improve headache symptoms, but it may not eliminate them entirely. Biofeedback-assisted relaxation training (BART) is considered safe and effective for reducing pain and medication use in migraine patients, and it is well-accepted, especially in children and adolescents. ^{1 2 3 6 7}

Is Amitriptyline, Biofeedback-Assisted Relaxation Training (BART), Cognitive Behavioral Therapy (CBT), or Cognitive Reappraisal Training (CR) a promising treatment for migraine?

Yes, these treatments are promising for migraine. Biofeedback-Assisted Relaxation Training (BART) helps reduce pain and medication use. Cognitive Behavioral Therapy (CBT) and Cognitive Reappraisal Training (CR) are effective in reducing headache frequency and improving coping skills. Combining these treatments with medication can enhance their positive effects. ^{2 5 8 9 10}

How does the Mind and Body Approaches for Migraine treatment differ from other migraine treatments?

This treatment is unique because it combines medication (Amitriptyline) with non-drug therapies like Biofeedback-Assisted Relaxation Training (BART) and Cognitive Behavioral Therapy (CBT), which have been shown to reduce migraine frequency and medication use by teaching patients to manage stress and change their thought patterns. ^{2 5 8 9 10}

Research Team

Scott Powers, PhD

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Robert Coghill, PhD

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Eligibility Criteria

This trial is for young people with migraines, who have them 8-28 days a month and experience some disruption in daily life. They must be able to swallow pills, not take certain painkillers too often, and can't start new migraine prevention meds during the study. Participants need to fit in an MRI scanner and not have metal implants or severe claustrophobia.

Inclusion Criteria

I have been diagnosed with migraine, following the ICHD-3b criteria.

My daily activities are mildly to severely disrupted due to my condition.

I have had between 8 and 28 headaches in the last 28 days.

Exclusion Criteria

You weigh less than 30 kg or more than 120 kg, or your size is not suitable for an MRI scanner.

I agree to limit my use of NSAIDs to less than 3 times a week and migraine medications to less than 6 times a month.

You have a psychiatric condition like psychosis, bipolar disorder, or major depression, or a developmental delay like autism or ADHD that could make it difficult to follow the study rules or participate safely.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive one of five treatments (CBT, BART, CR, amitriptyline, or placebo) over an 8-week period

8 weeks

Baseline and post-treatment assessments

Follow-up

Participants are monitored for changes in neural mechanisms and pain modulation after treatment

4 weeks

Treatment Details

Interventions

• Amitriptyline
• Biofeedback-Assisted Relaxation Training (BART)
• Cognitive Behavioral Therapy (CBT)
• Cognitive Reappraisal Training (CR)
• Placebo

Trial Overview The trial tests how well different treatments help youth with migraines by looking at brain scans, headache diaries, pain response tests, and questionnaires before/after treatment. Treatments include cognitive therapy (CBT), biofeedback training (BART), cognitive reappraisal (CR) training, amitriptyline (a medication), or placebo over 8 weeks.

Participant Groups

Group I: Cognitive Behavioral Therapy (CBT) Experimental Treatment 1 Intervention

Cognitive Behavioral Therapy (CBT) is a mind and body based intervention using education on gate control theory of pain, behavioral strategies such as muscle relaxation and activity pacing, and cognitive strategies including distraction, problem solving, and using calming self-statements.

Group II: Amitriptyline Active Control 1 Intervention

Amitriptyline will be administered once a day at home, to be taken by mouth. Dosage will be weight-based.

Group III: Biofeedback-Assisted Relaxation Training (BART) Active Control 1 Intervention

Biofeedback-Assisted Relaxation Training (BART) is a mind and body based intervention that focuses specifically on mind and body techniques such as deep breathing, muscle relaxation, and guided imagery skills to manage pain.

Group IV: Cognitive Retraining (CR) Active Control 1 Intervention

Cognitive Retraining (CR) is a mind and body based intervention that focuses on the use of tests of evidence and other cognitive strategies such as positive coping statements and pleasant activities and mindfulness to manage pain.

Group V: Placebo Placebo Group 1 Intervention

The placebo pill will be administered once a day at home, to be taken by mouth.

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

Approved in United States as Elavil for:

• Depression
• Anxiety and Stress
• Chronic Pain
• Fibromyalgia
• Headache
• Migraine Prevention
• Neuropathic Pain

Approved in European Union as Amitriptyline for:

• Depression
• Anxiety disorders
• Chronic pain
• Fibromyalgia
• Headache
• Migraine prevention
• Neuropathic pain

Approved in Canada as Elavil for:

• Depression
• Anxiety and stress
• Chronic pain
• Fibromyalgia
• Headache
• Migraine prevention
• Neuropathic pain

Who Is Running the Clinical Trial?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials

844

Recruited

6,566,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

National Center for Complementary and Integrative Health (NCCIH)

Collaborator

Trials

886

Recruited

677,000+

Findings from Research

Biofeedback-assisted relaxation training (BART) was effectively used in 61% of sessions with pediatric patients at Boston Children's Hospital, showing significant improvements in pain and mood ratings after treatment.

Patients experiencing both pain and anxiety benefited the most from BART, indicating its potential as a versatile treatment for various pediatric conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ready, set, relax: biofeedback-assisted relaxation training (BART) in a pediatric psychiatry consultation service. McKenna, K., Gallagher, KA., Forbes, PW., et al.[2016]

In a study of 23 patients with migraine headaches, those who received biofeedback-assisted relaxation therapy experienced greater reductions in pain and medication use compared to those who relaxed on their own.

The biofeedback group also showed significant decreases in cerebral blood flow velocity in the middle cerebral artery, indicating a potential mechanism for how this therapy alleviates migraine symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of biofeedback-assisted relaxation on migraine headache and changes in cerebral blood flow velocity in the middle cerebral artery. McGrady, A., Wauquier, A., McNeil, A., et al.[2019]

In a study of 41 patients with recurrent tension headaches, both cognitive-behavioral therapy (CBT) and amitriptyline showed significant improvements in headache activity, with CBT resulting in a 56% reduction in headache index compared to 27% for amitriptyline.

Cognitive-behavioral therapy was associated with more positive outcomes in certain areas, such as headache control and somatic complaints, although neither treatment completely eliminated headaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of pharmacological (amitriptyline HCL) and nonpharmacological (cognitive-behavioral) therapies for chronic tension headaches. Holroyd, KA., Nash, JM., Pingel, JD., et al.[2019]

Cognitive-behavioral therapy (CBT) was highly effective in reducing headache frequency, with an average reduction of 68% after 8 sessions, compared to 56% for biofeedback and only 20% for the control group.

Improvements from CBT continued to be observed at a 12-month follow-up, and the effectiveness of CBT was linked to participants' coping skills and social support, suggesting these factors may enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive-behavioral therapy versus temporal pulse amplitude biofeedback training for recurrent headache. Martin, PR., Forsyth, MR., Reece, J.[2018]

A study involving 76 patients with vascular headaches showed that a treatment program combining relaxation training and thermal biofeedback significantly reduced headache activity and medication use compared to a control group that only monitored headaches.

Both treatment groups, which received either minimal therapist contact or additional cognitive stress coping techniques, experienced similar benefits, indicating that the combination of relaxation and biofeedback is effective for managing headaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A controlled evaluation of the addition of cognitive therapy to a home-based biofeedback and relaxation treatment of vascular headache. Blanchard, EB., Appelbaum, KA., Nicholson, NL., et al.[2019]

In a study comparing relaxation training and amitriptyline for treating young patients with tension-type headaches, both treatments showed significant clinical improvement after 3 months, indicating their efficacy.

Relaxation therapy was found to be more accepted by patients than the medication, suggesting a preference for non-pharmacological approaches, although the study's preliminary nature and small sample size mean these conclusions should be viewed cautiously.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological behavioural treatment for children and adolescents with tension-type headache: preliminary data. Grazzi, L., Andrasik, F., Usai, S., et al.[2008]

In a follow-up study of 19 out of 21 migraine patients treated with either pharmacological (ergotamine) or nonpharmacological (relaxation and biofeedback) methods, both groups maintained a significant reduction in headache activity three years later.

Patients who received nonpharmacological treatment were less likely to require additional medical treatments compared to those treated with ergotamine, suggesting that nonpharmacological methods may lead to more sustainable long-term relief from migraines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term maintenance of improvements achieved with (abortive) pharmacological and nonpharmacological treatments for migraine: preliminary findings. Holroyd, KA., Holm, JF., Penzien, DB., et al.[2019]

In a study of 10 female patients with episodic common migraine, 16 sessions of electromyographic biofeedback combined with relaxation training led to a significant reduction in migraine episodes, with effects lasting up to 12 months after treatment.

The study found no direct correlation between electromyographic activity and pain levels, suggesting that factors like breathing control and muscle activity may play a key role in reducing migraine pain rather than just muscle tension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Italian experience of electromyographic-biofeedback treatment of episodic common migraine: preliminary results. Grazzi, L., Bussone, G.[2019]

Nonpharmacological treatments, such as relaxation techniques, endurance sports, biofeedback, and cognitive behavioral therapy, can effectively reduce the frequency of migraine attacks.

Consulting with a healthcare provider and combining these behavioral approaches with pharmacological treatments can enhance overall treatment effectiveness for migraine management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Relaxation techniques and behavioural therapy for the treatment of migraine : Guidelines from the German Migraine and Headache Society]. Kropp, P., Meyer, B., Dresler, T., et al.[2019]

In a study of 60 adults with migraines, those who underwent 8 weeks of mindfulness-based cognitive therapy for migraine (MBCT-M) showed a significant reduction in pain catastrophizing compared to a waitlist group, indicating the therapy's efficacy in addressing negative pain perceptions.

While pain catastrophizing decreased significantly, cognitive fusion did not show a notable change, suggesting that the reduction in pain-related distress may be a key mechanism through which MBCT-M improves migraine-related disability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in cognitive appraisal in a randomized controlled trial of mindfulness-based cognitive therapy for patients with migraine. Kruse, JA., Seng, EK.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Ready, set, relax: biofeedback-assisted relaxation training (BART) in a pediatric psychiatry consultation service. [2016]

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

Effect of biofeedback-assisted relaxation on migraine headache and changes in cerebral blood flow velocity in the middle cerebral artery. [2019]

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

A comparison of pharmacological (amitriptyline HCL) and nonpharmacological (cognitive-behavioral) therapies for chronic tension headaches. [2019]

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

Cognitive-behavioral therapy versus temporal pulse amplitude biofeedback training for recurrent headache. [2018]

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

A controlled evaluation of the addition of cognitive therapy to a home-based biofeedback and relaxation treatment of vascular headache. [2019]

6. Italy pubmed.ncbi.nlm.nih.gov

Pharmacological behavioural treatment for children and adolescents with tension-type headache: preliminary data. [2008]

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

Long-term maintenance of improvements achieved with (abortive) pharmacological and nonpharmacological treatments for migraine: preliminary findings. [2019]

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

Italian experience of electromyographic-biofeedback treatment of episodic common migraine: preliminary results. [2019]

9. Germany pubmed.ncbi.nlm.nih.gov

[Relaxation techniques and behavioural therapy for the treatment of migraine : Guidelines from the German Migraine and Headache Society]. [2019]

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

Changes in cognitive appraisal in a randomized controlled trial of mindfulness-based cognitive therapy for patients with migraine. [2023]