The anti-migraine activity of supplement formulation PEATONIDE® combining palmitoylethanolamide and melatonin
| ISRCTN | ISRCTN52370199 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN52370199 |
- Submission date
- 25/06/2024
- Registration date
- 06/08/2024
- Last edited
- 06/08/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nervous System Diseases
Plain English Summary
Background and study aims
Migraine represents a severe neurological condition, causing significant debilitation and pain for about 15% of the global population. As reported by the International Classification of Headache Disorders, episodic migraine manifests as acute headaches occurring on 14 or fewer days per month, while chronic migraines entail experiencing headaches on 15 or more days within a month. Migraine significantly affects the quality of life, ranking among the top 20 causes of disability in the adult population according to the World Health Organization. Despite the considerable impact on quality of life and decline in work performance and productivity, migraine often goes undiagnosed and untreated. Palmitoylethanolamide (PEA) and melatonin are thought to have anti-migraine activity through a synergistic effect leading to a reduction of vasodilation and thus the symptoms associated with migraine. This study aims to determine the effect and safety of treatment with a combination of hydrodispersible PEA and melatonin, as a supplement called PEATONIDE®, once a day in patients with episodic migraine, assessing both the duration and intensity of migraine attacks and the incidence of events and associated disability symptoms.
Who can participate?
Patients including both men and women aged 18 years old and over, with a diagnosis of episodic migraine (with or without aura) for at least one year before recruitment according to IHS-3 criteria and at least two migraine attacks for at least three months before recruitment.
What does the study involve?
Participants in the study will be given a supplement called PEATONIDE®, containing 1200 mg of hydrodispersible PEA and 0.2 mg of melatonin, or a placebo, to be taken orally every evening at bedtime for three months. During the study, participants will be allowed to use only acetaminophen and NSAIDs for acute migraine relief, with no other preventive or acute treatments permitted. Patients will record their migraine experiences in a daily headache diary, noting the number of migraine days per month, days using analgesics, intensity and duration of attacks, level of disability, presence of aura, and associated symptoms such as nausea, vomiting, sensitivity to light (photophobia), and sensitivity to sound (phonophobia). The intensity and disability of migraine attacks will be rated on a 10-point and a 3-point Likert psychometric scale scale, respectively.
What are the possible benefits and risks of participating?
Possible beneficial effects include the reduction of the number of monthly migraine attacks, the reduction of duration and intensity of migraine attacks, the reduction of the amount of medication for migraine management, and the reduction of the symptoms associated with migraine. Patients will be monitored for vital signs and adverse events to assess tolerability and safety.
Where is the study run from?
National Institute of Biostructures and Biosystems Inter-university Consortium (Istituto Nazionale Biostrutture e Biosistemi Consorzio Interuniversitario; I.N.B.B. Consortium)
When is the study starting and how long is it expected to run for?
February 2023 to April 2024
Who is funding the study?
Erbozeta S.p.A.
Who is the main contact?
Professor Giancarlo Tenore (University of Naples Federico II, Department of Pharmacy), giancarlo.tenore@unina.it
Contact information
Public, Scientific, Principal Investigator
Via Domenico Fontana 101
Napoli
80128
Italy
 ORCID ID |
0000-0002-0251-9936 |
|---|---|
| Phone | +39 339 877 64 88 |
| giancarlo.tenore@unina.it |
Study information
| Study design | Monocentric randomized placebo-controlled two parallel-arm study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised parallel trial |
| Study setting(s) | University/medical school/dental school |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | Anti-migraine activity of supplement formulation (PEATONIDE®) based on the synergic combination of palmitoylethanolamide and melatonin |
| Study acronym | AMSPM |
| Study hypothesis | Migraine pathophysiology is associated with mast cells, which act as the immediate call-center of the neuroimmune system. They represent both the source and target of several neuropeptides which are involved in migraine inflammatory process (e.g., histamine, serotonin, NO, prostaglandins, and leukotrienes). Therefore, mast cell degranulation inhibitors represent an innovative therapeutic approach for the prevention of migraine attacks. It was well reported that palmitoylethanolamide (PEA) and melatonin could contrast the immune response by down-regulating mast-cell degranulation. Therefore, the combination of the two molecules could increase the potential anti-migraine activity through a synergistic effect leading to a reduction of vasodilation and thus the symptoms associated with migraine. |
| Ethics approval(s) |
Approved 20/09/2023, Azienda sanitaria locale Napoli 1 Centro (Via Comunale del Principe, 13/a, Napoli, 80145, Italy; +39 0812541111; comitatoetico@aslnapoli1centro.it), ref: 1644 |
| Condition | Treatment of migraine attacks in subjects affected by episodic migraine (with or without aura) |
| Intervention | All included patients are treated with a formulation consisting of 1200 mg of hydrodispersible PEA and 0.2 mg of melatonin (PEATONIDE®) or with a placebo by oral administration taken every evening at bedtime for 3 months. The evaluation of migraine is based on the filling out of a daily headache diary. The headache diaries are administered during the two cycles of 4-week run-in periods and for three monthly cycles of treatment. After the two-month run-in period, the patients are randomly assigned to placebo or treated (PEATONIDE®) groups for the next three cycles. Participants will be randomised by the drawing of envelopes containing randomisation numbers. The random number list will be generated by an investigator with no clinical involvement in the trial. Data from the second cycle of the 4-week run-in period are averaged and served as baseline values. In the run-in and treatment cycles, the following variables are collected: number of days per month with migraine in the previous month; number of days per month taking any analgesic for migraine in the previous month; intensity, duration and grade of disability of migraine attacks; presence of aura; presence of associated symptoms (nausea, vomiting, photophobia, and phonophobia). The intensity and disability of migraine attacks are rated on a 10-point and a 3-point Likert scale, respectively. |
| Intervention type | Supplement |
| Primary outcome measure | Migraine frequency (days of migraine attacks per month) comparing the two-month run-in with the three-month treatment cycles measured using a headache diary daily |
| Secondary outcome measures | The following secondary outcome variables are assessed during the two-month run-in and the three-month treatment cycles: 1. The intensity of migraine attacks measured using a 10-point Likert scale for each migraine attack 2. Duration of migraine attacks measured in hours for each migraine attack 3. Grade of disability of migraine attack measured using a 3-point Likert scale for each migraine attack 4. The amount of analgesics used during migraine attacks measured as dose unit for each migraine attack |
| Overall study start date | 27/02/2023 |
| Overall study end date | 16/04/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 60 |
| Total final enrolment | 60 |
| Participant inclusion criteria | 1. Aged 18 years old and over 2. Diagnosis of episodic migraine (with or without aura) for at least one year before recruitment according to IHS-3 criteria 3. At least two migraine attacks for at least three months before recruitment |
| Participant exclusion criteria | 1. Inconsistent supplement intake 2. Regular uptake of analgesic drugs for more than 12 days per month 3. Treatment with other supplements, or drugs, potentially having preventive effects on migraine |
| Recruitment start date | 16/10/2023 |
| Recruitment end date | 16/11/2023 |
Locations
Countries of recruitment
- Italy
Study participating centre
Napoli
80126
Italy
Sponsor information
Industry
Strada delle Seriole, 41/43
Chiesanuova
SM03145
San Marino
| Phone | +39 0549 907000 |
|---|---|
| info@erbozeta.com | |
| Website | https://www.erbozeta.com/ |
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 29/07/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Planned publication in a peer-reviewed journal |
| IPD sharing plan | The datasets generated during the current study will be available upon request from Professor Giancarlo Tenore (University of Naples Federico II, Department of Pharmacy), giancarlo.tenore@unina.it. The data available are files (format Word) containing migraine diaries filled out by patients during the clinical trial. The timing for availability is 2 weeks. Consent from participants was required and obtained. |
Editorial Notes
11/07/2024: Study's existence from Erbozeta S.p.A.
