MigrainePhase 4NCT07856056
Nortriptyline Compared With Amitriptyline for Migraine Prevention at SQUH
A Phase 4 study testing Nortriptyline and Amitriptyline in people with Migraine, run by Sultan Qaboos University at 1 site in Oman.
Trial summary
This study will compare nortriptyline and amitriptyline for preventing migraine attacks in adults receiving care at Sultan Qaboos University Hospital in Oman. The researchers will assess whether the medicines differ in their effect on migraine frequency, side effects, and continued treatment use. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Migraine
- What is being tested?
- Nortriptyline and Amitriptyline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteOman
- Study dates
- May 2027to Dec 2030
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 to 65 years at consent, of any sex or nationality, receiving care at Sultan Qaboos University Hospital and able to attend the required visits.
- Migraine with or without aura diagnosed according to the International Classification of Headache Disorders, third edition, present for at least 12 months, with onset before age 50 years.
- A history consistent with episodic migraine during the preceding three months and a prospective baseline showing 4.0 to 14.0 migraine days inclusive and fewer than 15 headache days per 28 days.
- A clinical indication for preventive therapy agreed by the treating clinician and participant.
- At least 23 valid diary days during the prospective 28-day baseline. Frequency thresholds will be assessed using standardized 28-day counts without rounding.
- Ability to provide informed consent and complete an Arabic or English diary independently or with approved assistance that records the participant's own responses.
- For participants who could become pregnant, a negative pregnancy test and agreement to an effective contraceptive approach or consistent abstinence where this reflects usual practice, from consent until 30 days after the last study dose.
Who cannot join
- Chronic migraine, another predominant headache disorder, suspected secondary headache, a trigeminal autonomic cephalalgia, or inability to distinguish migraine from other recurrent head pain. Hemiplegic migraine and migraine with brainstem aura are excluded. Typical visual or sensory aura is eligible.
- Medication overuse headache or sustained acute medication use at overuse thresholds during the preceding three months. Use on 10 or more days per month of triptans, ergots, opioids, combination analgesics, or mixed acute drug classes, or on 15 or more days per month of simple analgesics or nonsteroidal anti-inflammatory drugs, will exclude participation. Baseline diary use meeting these thresholds will also exclude participation.
- Previous clear treatment failure after an adequate course of either trial medicine, or previous clinically important intolerance, allergy, or contraindication to either medicine or its excipients. An adequate course is at least eight weeks at a tolerated dose of at least 25 mg nightly with insufficient benefit. Brief previous exposure without established failure is permissible if completed at least three months before screening and recorded.
- Current migraine preventive medication or another treatment with substantial preventive activity that cannot safely be stopped. Oral preventive medicines must have been discontinued for at least four weeks and at least five elimination half-lives, whichever is longer, before baseline. OnabotulinumtoxinA or peripheral nerve blocks for prevention within four months, or a calcitonin gene-related peptide monoclonal antibody within six months or five half-lives, whichever is longer, will exclude participation. Preventive gepants follow the oral preventive washout rule. Effective treatment will not be withdrawn solely to enable enrollment when clinically inappropriate.
- Current use of another antidepressant, a monoamine oxidase inhibitor, or a clinically important interacting medicine that cannot safely be avoided. All prescribed, nonprescribed, and herbal products will undergo pharmacist review. A prior monoamine oxidase inhibitor requires at least a 14-day interval, with any longer product-specific interval respected. Recent fluoxetine or another long-acting inhibitor requires an individualized documented washout. Psychiatric treatment will not be withdrawn simply to meet trial eligibility.
- Previous myocardial infarction with ongoing risk, clinically significant ischemic or structural heart disease, heart failure, clinically important arrhythmia, unexplained syncope, congenital long QT syndrome, Brugada syndrome, or a family history suggesting an inherited arrhythmia without satisfactory specialist assessment.
Show all 14Show fewer
- Baseline corrected QT interval using Fridericia's formula above 450 milliseconds in men or 470 milliseconds in women, QRS duration of 120 milliseconds or greater, any degree of atrioventricular block including PR above 200 milliseconds, or another clinically significant electrocardiographic abnormality. A borderline or technically inadequate trace may be repeated and reviewed before eligibility is determined.
- Uncontrolled epilepsy, previous serious drug-related seizure, untreated narrow-angle glaucoma, clinically important urinary retention, paralytic ileus, untreated hyperthyroidism, or a comparable condition increasing tricyclic treatment risk.
- Severe hepatic disease, estimated glomerular filtration rate below 30 mL/min/1.73 m², or clinically significant uncorrected electrolyte disturbance. Alanine aminotransferase or aspartate aminotransferase above three times the local upper limit, or bilirubin above twice the upper limit unless a documented benign cause exists, requires exclusion or specialist clarification before reconsideration.
- Bipolar I or II disorder, previous antidepressant-induced mania or hypomania, current psychosis, current suicidal intent or plan, a suicide attempt within the preceding year, or another psychiatric condition requiring treatment incompatible with the protocol. Stable anxiety or mild depressive symptoms alone will not exclude participation.
- Current moderate or severe substance use disorder likely to affect safety or reliable participation.
- Pregnancy, breastfeeding, planned pregnancy during participation, or inability to follow the agreed pregnancy prevention arrangements.
- Participation in another interventional trial within the preceding 30 days or five investigational drug half-lives, whichever is longer.
- A condition, planned procedure, or practical limitation preventing informed consent, reliable outcome assessment, or safe completion, with a specific reason documented by the investigator.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Oman1 site
Sultan Qaboos University Hospital, University Medical City
Muscat
Mohammed Al.Alawi, 24 147777, m.alalawi2@squ.edu.om
About this study
Official title: A Randomized Double Blind Parallel Group Trial Comparing Nortriptyline With Amitriptyline for the Preventive Treatment of Episodic Migraine in Adults at Sultan Qaboos University Hospital
This study will compare nortriptyline and amitriptyline for preventing migraine attacks in adults receiving care at Sultan Qaboos University Hospital in Oman. The researchers will assess whether the medicines differ in their effect on migraine frequency, side effects, and continued treatment use.
Ninety adults with episodic migraine will be assigned by chance to receive either nortriptyline or amitriptyline, with 45 participants in each group. After completing a four-week baseline headache diary, participants will take the assigned medicine each evening for 16 weeks. Treatment will start at 10 mg nightly and increase gradually toward 50 mg nightly when tolerated. Lower doses will be permitted for safety or tolerability reasons. Participants and the clinical assessment team will not know which medicine has been assigned.
Read more
The main outcome will be the change in migraine days during the final four weeks of treatment compared with baseline. Other outcomes will include headache days, use of medicines for acute headache, headache impact, migraine-related disability, adverse events, and stopping treatment because of adverse events.
Treatment will usually be tapered over two weeks, with a final safety assessment at week 20 after randomization. Participation will last approximately 24 weeks, including the baseline period. Appropriate acute migraine treatment will remain available throughout the study.
Read the detailed description
This investigator-initiated, single-centre, randomized, blinded, active-comparator, parallel-group superiority trial will compare nortriptyline with amitriptyline for the preventive treatment of episodic migraine at Sultan Qaboos University Hospital, Muscat, Oman.
Adults aged 18 to 65 years with migraine with or without aura will be screened. Eligibility requires a history consistent with episodic migraine and a prospective 28-day baseline showing 4 to 14 migraine days and fewer than 15 headache days, with at least 23 valid diary days.
Ninety participants will be randomized in a 1:1 ratio. An independent statistician will generate an unstratified allocation sequence using randomly varying balanced permuted blocks. Allocation will be concealed through a pharmacy-controlled system. Participants, care providers, investigators, and outcome assessors will remain masked. Pharmacy personnel preparing the medicines and the statistician generating the allocation sequence will be unmasked.
The medicines will be supplied in matching coded capsules containing 10 mg of the assigned medicine. The planned dose is 10 mg nightly during week 1, 20 mg during week 2, 30 mg during week 3, and 40 mg during week 4. The target from week 5 is 50 mg nightly when tolerated. Lower maintenance doses, temporary holds, reductions, or discontinuation are permitted for documented safety or tolerability reasons. Early subjective improvement alone will not determine a lower target during scheduled titration. Participants may decline escalation or stop treatment while continuing outcome follow-up.
The final tolerated maintenance dose will be documented by week 6, with no routine escalation after day 42. Equal numerical doses are not assumed to be pharmacologically equivalent. The trial compares these specified treatment strategies.
The randomized treatment period is 16 weeks. Randomization defines study day 1, and delayed treatment initiation or visits will not shift outcome windows. The primary endpoint period is days 85 to 112. Treatment will normally be tapered over the following two weeks, with a safety assessment at week 20. Appropriate ongoing migraine care will be arranged.
The primary outcome is change from baseline in migraine days per 28 days during weeks 13 to 16. Secondary outcomes include the proportion achieving at least a 50% reduction in migraine days, changes in headache days and acute headache medication days, Headache Impact Test scores, Migraine Disability Assessment scores, treatment discontinuation because of adverse events, adverse events, serious adverse events, and body weight.
Safety procedures include clinical assessment, electrocardiograms, relevant laboratory tests, medication interaction review, pregnancy testing where applicable, and psychiatric risk assessment. An independent safety physician will review emerging safety information.
The sample size uses planning assumptions of a between-group difference of 2 migraine days per 28 days, a standard deviation of 3 days, 80% power, and a two-sided significance level of 0.05. Approximately 37 evaluable participants per group are required. Allowance for approximately 15% unavailable primary outcomes and rounding gives a target of 90 randomized participants.
The primary analysis will follow the intention-to-treat principle and use analysis of covariance adjusted for baseline migraine days. The adjusted between-group difference will be reported with a 95% confidence interval. Missing outcomes will be addressed using prespecified multiple imputation and sensitivity analyses. Secondary analyses will be exploratory. A nonsignificant difference will not establish equivalence or noninferiority.
Ethical approval will be sought from the Medical Research Ethics Committee, College of Medicine and Health Sciences, Sultan Qaboos University. Recruitment will begin only after ethics approval and other required institutional and regulatory permissions are obtained.
- Conditions
- Migraine
- Being tested
- Nortriptyline, Amitriptyline
- Keywords
- Episodic migraine, Migraine prevention, Nortriptyline, Amitriptyline
- Medical subject headings
- Migraine Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NortriptylineDrug
Oral nortriptyline supplied in matching coded 10 mg capsules. Participants will take one to five capsules nightly according to the prescribed schedule, starting at 10 mg and increasing no more frequently than weekly toward 50 mg when tolerated. Dose adjustments will follow prespecified safety and tolerability rules. The randomized treatment period is 16 weeks, normally followed by an individualized taper over approximately two weeks.
AmitriptylineDrug
Oral amitriptyline supplied in matching coded 10 mg capsules. Participants will take one to five capsules nightly according to the prescribed schedule, starting at 10 mg and increasing no more frequently than weekly toward 50 mg when tolerated. Dose adjustments will follow prespecified safety and tolerability rules. The randomized treatment period is 16 weeks, normally followed by an individualized taper over approximately two weeks.
| Study group | Role | What they receive |
|---|---|---|
| Nortriptyline | Experimental | Participants will receive oral nortriptyline each evening for 16 weeks. The planned dose is 10 mg nightly in week 1, 20 mg in week 2, 30 mg in week 3, and 40 mg in week 4, followed by a target of 50 mg nightly from week 5 when tolerated. Lower doses and treatment interruptions are permitted for safety or tolerability. The final maintenance dose will be documented by week 6, with no routine escalation after day 42. Treatment will normally be tapered after week 16, with safety follow-up at week 20. Receives: Drug: Nortriptyline |
| Amitriptyline | Active comparator | Participants will receive oral amitriptyline each evening for 16 weeks. The planned dose is 10 mg nightly in week 1, 20 mg in week 2, 30 mg in week 3, and 40 mg in week 4, followed by a target of 50 mg nightly from week 5 when tolerated. Lower doses and treatment interruptions are permitted for safety or tolerability. The final maintenance dose will be documented by week 6, with no routine escalation after day 42. Treatment will normally be tapered after week 16, with safety follow-up at week 20. Receives: Drug: Amitriptyline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Migraine Days per 28 Days During Weeks 13 to 16
Migraine days will be measured using a daily diary. A qualifying day contains headache lasting at least 30 minutes with migraine or probable migraine features, or qualifying headache accompanying previously confirmed typical aura. Headache successfully treated with a migraine-specific acute medicine also qualifies, including when shorter than 30 minutes. Aura without headache is excluded. Successful acute treatment means improvement within two hours from moderate or severe pain to mild or no pain, or from mild pain to no pain. Multiple qualifying attacks on one day count once. For periods with at least 23 valid days, counts will be standardized to 28 days. Change is the count during days 85 to 112 minus the prospective baseline count. Negative values indicate improvement.
Measured: Baseline, the 28 days before randomization, and weeks 13 to 16 after randomization, days 85 to 112
Secondary outcomes (6)
Percentage of Participants With at Least a 50% Reduction in Migraine Days
Percentage of participants whose standardized migraine day count during days 85 to 112 is at least 50% lower than their prospective baseline count. A higher percentage indicates a greater treatment response.
Measured: Baseline, the 28 days before randomization, and weeks 13 to 16 after randomization
Change From Baseline in Acute Headache Medication Days per 28 Days
An acute headache medication day is a day on which at least one medicine is taken to treat headache. Multiple doses or medicines on the same day count once. Counts from periods with at least 23 valid diary days will be standardized to 28 days. Change is the count during days 85 to 112 minus baseline. Negative values indicate reduced acute medication use.
Measured: Baseline, the 28 days before randomization, and weeks 13 to 16 after randomization
Change From Baseline in Headache Impact Test Total Score
The six-item Headache Impact Test, HIT-6, measures the impact of headache on daily life. Total scores range from 36 to 78, with higher scores indicating greater headache impact. Change will be calculated as the week 16 score minus the baseline score. Negative values indicate improvement.
Measured: Baseline and week 16 after randomization
Change From Baseline in Migraine Disability Assessment Total Score
The Migraine Disability Assessment, MIDAS, measures headache-related disability during the preceding three months. The total is the sum of five disability items covering work or school, household work, and family, social, or leisure activities. The minimum score is 0, and higher scores indicate greater disability. The total is not normalized to a 0 to 100 scale. Change will be calculated as the week 16 score minus the baseline score. Negative values indicate improvement.
Measured: Baseline and week 16 after randomization
Percentage of Participants Discontinuing Assigned Treatment Because of an Adverse Event
Percentage of participants who permanently discontinue their assigned study medicine because of an adverse event during the randomized treatment period. Medication discontinuation will be distinguished from withdrawal from outcome follow-up.
Measured: From the first study dose through day 112 after randomization
Percentage of Participants With Treatment-Emergent Adverse Events
Percentage of participants experiencing at least one new medical event or worsening of a pre-existing event after starting study medication, regardless of its assessed relationship to treatment. Events will be assessed for severity, seriousness, relationship to treatment, and outcome.
Measured: From the first study dose through day 140 after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2026
- Study startMay 2027 (estimated)
- Primary completionMay 2030 (estimated)
- Study completionDec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for MigraineStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sultan Qaboos University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mohammed Al Alawi MD PhD MRCPsych ARABpsych OMSBpsych, Sultan Qaboos University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07856056
- Sponsor's protocol ID
- SQUH MIG TCA 01
- Status last verified
- Sep 2026
- First submitted
- 27 Sep 2026
- Last updated
- 2 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: A controlled-access individual participant data sharing plan is proposed but has not yet been finalized. The proposed plan would make a deidentified analysis dataset and data dictionary available to researchers with a scientifically justified request, subject to institutional and ethics permission and a signed data use agreement. Direct identifiers and source medical records would not be shared. The final plan will be aligned with the approved consent documents and institutional requirements and updated in the registry before participant enrollment.
Publications
Roghani M, Ghaedi G, Iranzadeh S, Golezar MH, Afshinmajd S. Efficacy and safety of venlafaxine versus nortriptyline for the preventive treatment of migraine: A double-blind randomized clinical trial. Clin Neurol Neurosurg. 2024 Aug;243:108400. doi: 10.1016/j.clineuro.2024.108400. Epub 2024 Jun 17.
PubMed 38901375Goncalves AL, Martini Ferreira A, Ribeiro RT, Zukerman E, Cipolla-Neto J, Peres MF. Randomised clinical trial comparing melatonin 3 mg, amitriptyline 25 mg and placebo for migraine prevention. J Neurol Neurosurg Psychiatry. 2016 Oct;87(10):1127-32. doi: 10.1136/jnnp-2016-313458. Epub 2016 May 10.
PubMed 27165014Diener HC, Tassorelli C, Dodick DW, Silberstein SD, Lipton RB, Ashina M, Becker WJ, Ferrari MD, Goadsby PJ, Pozo-Rosich P, Wang SJ, Houle TT, Hoek TCVD, Martinelli D, Terwindt GM; International Headache Society Clinical Trials Committee. Guidelines of the International Headache Society for controlled trials of preventive treatment of migraine attacks in episodic migraine in adults. Cephalalgia. 2020 Sep;40(10):1026-1044. doi: 10.1177/0333102420941839. Epub 2020 Jul 28.
PubMed 32722936
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Double Blind Parallel Group Trial Comparing Nortriptyline With Amitriptyline for the Preventive Treatment of Episodic Migraine in Adults at Sultan Qaboos University Hospital
- ClinicalTrials.gov ID
- NCT07856056
- Acronym / sponsor ID
- SQUH MIG TCA 01
- Conditions
- Migraine
- Keywords
- Episodic migraine, Migraine prevention, Nortriptyline, Amitriptyline
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Sultan Qaboos UniversityUniversity, hospital or other
- Study start
- May 2027 (estimated)
- Primary completion
- May 2030 (estimated)
- Study completion
- Dec 2030 (estimated)
- First posted
- 2 Oct 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will compare nortriptyline and amitriptyline for preventing migraine attacks in adults receiving care at Sultan Qaboos University Hospital in Oman. The researchers will assess whether the medicines differ in their effect on migraine frequency, side effects, and continued treatment use.
Ninety adults with episodic migraine will be assigned by chance to receive either nortriptyline or amitriptyline, with 45 participants in each group. After completing a four-week baseline headache diary, participants will take the assigned medicine each evening for 16 weeks. Treatment will start at 10 mg nightly and increase gradually toward 50 mg nightly when tolerated. Lower doses will be permitted for safety or tolerability reasons. Participants and the clinical assessment team will not know which medicine has been assigned.
The main outcome will be the change in migraine days during the final four weeks of treatment compared with baseline. Other outcomes will include headache days, use of medicines for acute headache, headache impact, migraine-related disability, adverse events, and stopping treatment because of adverse events.
Treatment will usually be tapered over two weeks, with a final safety assessment at week 20 after randomization. Participation will last approximately 24 weeks, including the baseline period. Appropriate acute migraine treatment will remain available throughout the study.
Detailed description
This investigator-initiated, single-centre, randomized, blinded, active-comparator, parallel-group superiority trial will compare nortriptyline with amitriptyline for the preventive treatment of episodic migraine at Sultan Qaboos University Hospital, Muscat, Oman.
Adults aged 18 to 65 years with migraine with or without aura will be screened. Eligibility requires a history consistent with episodic migraine and a prospective 28-day baseline showing 4 to 14 migraine days and fewer than 15 headache days, with at least 23 valid diary days.
Ninety participants will be randomized in a 1:1 ratio. An independent statistician will generate an unstratified allocation sequence using randomly varying balanced permuted blocks. Allocation will be concealed through a pharmacy-controlled system. Participants, care providers, investigators, and outcome assessors will remain masked. Pharmacy personnel preparing the medicines and the statistician generating the allocation sequence will be unmasked.
The medicines will be supplied in matching coded capsules containing 10 mg of the assigned medicine. The planned dose is 10 mg nightly during week 1, 20 mg during week 2, 30 mg during week 3, and 40 mg during week 4. The target from week 5 is 50 mg nightly when tolerated. Lower maintenance doses, temporary holds, reductions, or discontinuation are permitted for documented safety or tolerability reasons. Early subjective improvement alone will not determine a lower target during scheduled titration. Participants may decline escalation or stop treatment while continuing outcome follow-up.
The final tolerated maintenance dose will be documented by week 6, with no routine escalation after day 42. Equal numerical doses are not assumed to be pharmacologically equivalent. The trial compares these specified treatment strategies.
The randomized treatment period is 16 weeks. Randomization defines study day 1, and delayed treatment initiation or visits will not shift outcome windows. The primary endpoint period is days 85 to 112. Treatment will normally be tapered over the following two weeks, with a safety assessment at week 20. Appropriate ongoing migraine care will be arranged.
The primary outcome is change from baseline in migraine days per 28 days during weeks 13 to 16. Secondary outcomes include the proportion achieving at least a 50% reduction in migraine days, changes in headache days and acute headache medication days, Headache Impact Test scores, Migraine Disability Assessment scores, treatment discontinuation because of adverse events, adverse events, serious adverse events, and body weight.
Safety procedures include clinical assessment, electrocardiograms, relevant laboratory tests, medication interaction review, pregnancy testing where applicable, and psychiatric risk assessment. An independent safety physician will review emerging safety information.
The sample size uses planning assumptions of a between-group difference of 2 migraine days per 28 days, a standard deviation of 3 days, 80% power, and a two-sided significance level of 0.05. Approximately 37 evaluable participants per group are required. Allowance for approximately 15% unavailable primary outcomes and rounding gives a target of 90 randomized participants.
The primary analysis will follow the intention-to-treat principle and use analysis of covariance adjusted for baseline migraine days. The adjusted between-group difference will be reported with a 95% confidence interval. Missing outcomes will be addressed using prespecified multiple imputation and sensitivity analyses. Secondary analyses will be exploratory. A nonsignificant difference will not establish equivalence or noninferiority.
Ethical approval will be sought from the Medical Research Ethics Committee, College of Medicine and Health Sciences, Sultan Qaboos University. Recruitment will begin only after ethics approval and other required institutional and regulatory permissions are obtained.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nortriptyline | Experimental | Drug: NortriptylineParticipants will receive oral nortriptyline each evening for 16 weeks. The planned dose is 10 mg nightly in week 1, 20 mg in week 2, 30 mg in week 3, and 40 mg in week 4, followed by a target of 50 mg nightly from week 5 when tolerated. Lower doses and treatment interruptions are permitted for safety or tolerability. The final maintenance dose will be documented by week 6, with no routine escalation after day 42. Treatment will normally be tapered after week 16, with safety follow-up at week 20. |
| Amitriptyline | Active comparator | Drug: AmitriptylineParticipants will receive oral amitriptyline each evening for 16 weeks. The planned dose is 10 mg nightly in week 1, 20 mg in week 2, 30 mg in week 3, and 40 mg in week 4, followed by a target of 50 mg nightly from week 5 when tolerated. Lower doses and treatment interruptions are permitted for safety or tolerability. The final maintenance dose will be documented by week 6, with no routine escalation after day 42. Treatment will normally be tapered after week 16, with safety follow-up at week 20. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age 18 to 65 years at consent, of any sex or nationality, receiving care at Sultan Qaboos University Hospital and able to attend the required visits.
- Migraine with or without aura diagnosed according to the International Classification of Headache Disorders, third edition, present for at least 12 months, with onset before age 50 years.
- A history consistent with episodic migraine during the preceding three months and a prospective baseline showing 4.0 to 14.0 migraine days inclusive and fewer than 15 headache days per 28 days.
- A clinical indication for preventive therapy agreed by the treating clinician and participant.
- At least 23 valid diary days during the prospective 28-day baseline. Frequency thresholds will be assessed using standardized 28-day counts without rounding.
Key exclusion criteria (14 listed)
- Chronic migraine, another predominant headache disorder, suspected secondary headache, a trigeminal autonomic cephalalgia, or inability to distinguish migraine from other recurrent head pain. Hemiplegic migraine and migraine with brainstem aura are excluded. Typical visual or sensory aura is eligible.
- Medication overuse headache or sustained acute medication use at overuse thresholds during the preceding three months. Use on 10 or more days per month of triptans, ergots, opioids, combination analgesics, or mixed acute drug classes, or on 15 or more days per month of simple analgesics or nonsteroidal anti-inflammatory drugs, will exclude participation. Baseline diary use meeting these thresholds will also exclude participation.
- Previous clear treatment failure after an adequate course of either trial medicine, or previous clinically important intolerance, allergy, or contraindication to either medicine or its excipients. An adequate course is at least eight weeks at a tolerated dose of at least 25 mg nightly with insufficient benefit. Brief previous exposure without established failure is permissible if completed at least three months before screening and recorded.
- Current migraine preventive medication or another treatment with substantial preventive activity that cannot safely be stopped. Oral preventive medicines must have been discontinued for at least four weeks and at least five elimination half-lives, whichever is longer, before baseline. OnabotulinumtoxinA or peripheral nerve blocks for prevention within four months, or a calcitonin gene-related peptide monoclonal antibody within six months or five half-lives, whichever is longer, will exclude participation. Preventive gepants follow the oral preventive washout rule. Effective treatment will not be withdrawn solely to enable enrollment when clinically inappropriate.
- Current use of another antidepressant, a monoamine oxidase inhibitor, or a clinically important interacting medicine that cannot safely be avoided. All prescribed, nonprescribed, and herbal products will undergo pharmacist review. A prior monoamine oxidase inhibitor requires at least a 14-day interval, with any longer product-specific interval respected. Recent fluoxetine or another long-acting inhibitor requires an individualized documented washout. Psychiatric treatment will not be withdrawn simply to meet trial eligibility.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NortriptylineOral nortriptyline supplied in matching coded 10 mg capsules. Participants will take one to five capsules nightly according to the prescribed schedule, starting at 10 mg and increasing no more frequently than weekly toward 50 mg when tolerated. Dose adjustments will follow prespecified safety and tolerability rules. The randomized treatment period is 16 weeks, normally followed by an individualized taper over approximately two weeks. | Drug | Nortriptyline |
| AmitriptylineOral amitriptyline supplied in matching coded 10 mg capsules. Participants will take one to five capsules nightly according to the prescribed schedule, starting at 10 mg and increasing no more frequently than weekly toward 50 mg when tolerated. Dose adjustments will follow prespecified safety and tolerability rules. The randomized treatment period is 16 weeks, normally followed by an individualized taper over approximately two weeks. | Drug | Amitriptyline |
Primary outcome
Change From Baseline in Migraine Days per 28 Days During Weeks 13 to 16
Time frame: Baseline, the 28 days before randomization, and weeks 13 to 16 after randomization, days 85 to 112
Migraine days will be measured using a daily diary. A qualifying day contains headache lasting at least 30 minutes with migraine or probable migraine features, or qualifying headache accompanying previously confirmed typical aura. Headache successfully treated with a migraine-specific acute medicine also qualifies, including when shorter than 30 minutes. Aura without headache is excluded. Successful acute treatment means improvement within two hours from moderate or severe pain to mild or no pain, or from mild pain to no pain. Multiple qualifying attacks on one day count once. For periods with at least 23 valid days, counts will be standardized to 28 days. Change is the count during days 85 to 112 minus the prospective baseline count. Negative values indicate improvement.
6 secondary outcomes
Percentage of Participants With at Least a 50% Reduction in Migraine Days
Time frame: Baseline, the 28 days before randomization, and weeks 13 to 16 after randomization
Change From Baseline in Acute Headache Medication Days per 28 Days
Time frame: Baseline, the 28 days before randomization, and weeks 13 to 16 after randomization
Change From Baseline in Headache Impact Test Total Score
Time frame: Baseline and week 16 after randomization
Change From Baseline in Migraine Disability Assessment Total Score
Time frame: Baseline and week 16 after randomization
Percentage of Participants Discontinuing Assigned Treatment Because of an Adverse Event
Time frame: From the first study dose through day 112 after randomization
Percentage of Participants With Treatment-Emergent Adverse Events
Time frame: From the first study dose through day 140 after randomization
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2026.
- Background: PubMed 38901375Roghani M, Ghaedi G, Iranzadeh S, Golezar MH, Afshinmajd S. Efficacy and safety of venlafaxine versus nortriptyline for the preventive treatment of migraine: A double-blind randomized clinical trial. Clin Neurol Neurosurg. 2024 Aug;243:108400. doi: 10.1016/j.clineuro.2024.108400. Epub 2024 Jun 17.
- Background: PubMed 27165014Goncalves AL, Martini Ferreira A, Ribeiro RT, Zukerman E, Cipolla-Neto J, Peres MF. Randomised clinical trial comparing melatonin 3 mg, amitriptyline 25 mg and placebo for migraine prevention. J Neurol Neurosurg Psychiatry. 2016 Oct;87(10):1127-32. doi: 10.1136/jnnp-2016-313458. Epub 2016 May 10.
- Background: PubMed 32722936Diener HC, Tassorelli C, Dodick DW, Silberstein SD, Lipton RB, Ashina M, Becker WJ, Ferrari MD, Goadsby PJ, Pozo-Rosich P, Wang SJ, Houle TT, Hoek TCVD, Martinelli D, Terwindt GM; International Headache Society Clinical Trials Committee. Guidelines of the International Headache Society for controlled trials of preventive treatment of migraine attacks in episodic migraine in adults. Cephalalgia. 2020 Sep;40(10):1026-1044. doi: 10.1177/0333102420941839. Epub 2020 Jul 28.
- Individual participant dataSharing planned: Undecided. A controlled-access individual participant data sharing plan is proposed but has not yet been finalized. The proposed plan would make a deidentified analysis dataset and data dictionary available to researchers with a scientifically justified request, subject to institutional and ethics permission and a signed data use agreement. Direct identifiers and source medical records would not be shared. The final plan will be aligned with the approved consent documents and institutional requirements and updated in the registry before participant enrollment.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Nortriptyline and Amitriptyline in people with Migraine, run by Sultan Qaboos University at 1 site in Oman.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 2 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Oman. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mohammed Al.Alawi, MD, PhD, MBA, MRCPsych UK (96824141511, m.alalawi2@squ.edu.om), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Migraine Days per 28 Days During Weeks 13 to 16 (time frame: Baseline, the 28 days before randomization, and weeks 13 to 16 after randomization, days 85 to 112). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07856056, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2026.