Clinical trials-Phase II
In this phase, 237 patients have been treated by Migraine Spray. Patients referring to the migraine clinic are examined by a Neurologist. Also, the patients’ medical records and information related to headache symptoms are collected. By comparing the symptoms with the migraine diagnostic criteria defined by the International Headache Society (IHS), patients without migraine symptoms are excluded. Also, if necessary, further tests by Computerized Tomography (CT) and Magnetic Resonance Imaging (MRI) scans are used to confirm the diagnosis. Finally, the medical records of patients with confirmed migraine headache are filed.
The migraine patients are oriented to be treated by Migraine Spray. They are instructed about the treatment period, timetable, receiving medication, headache indices, how to fill daily forms and inclusion criteria (Appendix IV). Upon written acceptance by the patient, he/she enters into treatment. The dose of medication for each individual is determined due to her/his weight (per kg). The treatment includes 20 sessions of taking medication via inhaling. Based on three treatment protocols, treatment by Migraine Spraylasts between 3 to 5 weeks. The sessions are scheduled so that each week includes at least 4 sessions and there are no more than 6 days of delay between every two successive sessions. Inhaling is performed in a special apparatus designed by a group of medical engineers.
The patients under treatment enter the data on migraine attacks in a diary form (Appendix V). These daily reports are also crosschecked by a nurse of the clinic in each treatment session (Appendix VI). After completion of the treatment sessions, a doctor re-examines the patient and evaluate his/her daily records. Then, a follow-up plan is arranged. In this plan, the patient is instructed to fill up the forms to report any future headaches. Based on the records, the doctor may advise a patient to retake Migraine Spraying some “once per month” treatment sessions, which is called “recall sessions”. These sessions may be repeated from 1 to 4 months and for very special cases, even up to the 8th month, due to the doctor’s decision. More than half of the patients received medication at most two “recall” sessions.
A significant number of patients treated by Migraine Spray do not feel as migraineurs and are satisfied with their after-treatment conditions, are reluctant to fill up daily forms and to provide requested data during the follow-up period. They feel filling up forms of daily conditions as a burden. This obstacle partially depends on the psychology of migraineurs. On the contrary, the small numbers of the patients (less than 10 percent) who need more treatment, periodically come for “recall” treatment sessions and fill-up the forms. Consequently, a thorough data collection of the treated migraineurs has been restricted.
Migraine Spray, as a powder, required to be processed and used in special inhaling apparatus in professional pain clinics. These constraints were some barriers to easy treatment of migraine patients. An R&D team including some experts in biophysics, biochemistry, cell-biology and pharmacy have focused on research and develop an easy-to-use shape of the drug. Finally, they have developed Migraine Spray®, as a nasal spray.
Theoretically speaking, during the treatments by Migraine Spray® or Migraine Spray® the nasal mucous membrane of the patients absorbs the active constituents of the drug. The inhaling apparatus was already designed to absorb a certain amount of the active constituents of the drug. Since the curative treatments of the migraineurs were very promising in Phase I is has been a base for designing the nasal spray. That is, theoretically, Migraine Spray®, as a nasal spray, functions similar to the inhaling apparatus.
In Phase II, by developing the nasal spray, both Migraine Spray and Migraine Sprayhave been advised to the patients, in parallel. The treatment by either shape of the drug was depending upon the patients’ choices. The curative results of the clinical trials also have confirmed the theoretical considerations.
IHS indices of migraine headaches
To assess the severity of migraine headache, three following indices were defined: number of attacks, duration of headache, and pain intensity of attacks in each period (i.e., per month). These indices were calculated for each patient as described below.
- Frequency of attacks: This index is the number of attacks in a one-month period based on IHS characteristics of migraine headaches. Those headaches that are diagnosed as non-migraine ones (such as attacks that are triggered by psychological stress, common cold, and so on) are not calculated.
- Duration of headache: Duration of each attack is the time difference between its beginning and its end, calculated in hours. Those headaches that last for more than one day are considered as one attack with long durations. This index is the average duration of the migraine attacks during a given period (i.e., the sum of headaches duration is divided by the number of headaches.).
- Pain intensity of attack: Pain intensity of each attack is evaluated by each patient according to her/his feelings, using a 10-point scale. Number 1 is assigned to a very mild attack and 10 to a severe attack which prevents the patients from performing daily activities. This index is the average pain intensity of the migraine attacks during a given period (i.e., the sum of headaches pain intensity is divided by the number of headaches in a month).