Trial Outcomes & Findings for Effectiveness of Onabotulinumtoxin A (Botox) in Pediatric Patients Experiencing Migraines: A Study in the Pediatric Pain Population (NCT NCT03055767)

NCT ID: NCT03055767

Last Updated: 2023-10-18

Results Overview

The frequency of migraines in days.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 17 participants
• Primary outcome timeframe: Baseline (4 weeks) and 12 weeks post each, respective intervention
• Results posted on: 2023-10-18

Participant Flow

Pediatric subjects aged 8 to 17 were recruited during an enrollment window from March 1st, 2017 to November 30th, 2018 at the UCI Health Center for Pain and Wellness located at UCI Health's Gottschalk Medical Plaza.

Participant milestones

Measure	Cross-over: OnabotulinumtoxinA, Then Saline Placebo The AB subject group will receive OnabotulinumtoxinA in the first treatment and saline placebo in the second. Both groups will then receive OnabotulinumtoxinA in the last two treatments. There will be one treatment at the beginning of each 12 week block, meaning 4 treatments over the 48 week study period total. Progress check-ups will occur every 6 weeks during the study. Randomization will be via selection of sealed envelope.	Cross-over: Saline Placebo, Then OnabotulinumtoxinA The BA subject group will receive saline and then Onabotulinumtoxin. A.Both groups will then receive OnabotulinumtoxinA in the last two treatments. There will be one treatment at the beginning of each 12 week block, meaning 4 treatments over the 48 week study period total. Progress check-ups will occur every 6 weeks during the study. Randomization will be via selection of sealed envelope.	Open Label Botox Following unblinding, subject elected Botox treatment for 24 week open-label period where all subjects receive Botox treatment.	Open Label Standard of Care Following unblinding, subject elected to a 24-week return to conservative management per standard-of-care protocols.
Double-Blind Period STARTED	9	6	0	0
Double-Blind Period COMPLETED	9	6	0	0
Double-Blind Period NOT COMPLETED	0	0	0	0
Open-Label Period STARTED	0	0	11	4
Open-Label Period COMPLETED	0	0	9	3
Open-Label Period NOT COMPLETED	0	0	2	1

Reasons for withdrawal

Measure	Cross-over: OnabotulinumtoxinA, Then Saline Placebo The AB subject group will receive OnabotulinumtoxinA in the first treatment and saline placebo in the second. Both groups will then receive OnabotulinumtoxinA in the last two treatments. There will be one treatment at the beginning of each 12 week block, meaning 4 treatments over the 48 week study period total. Progress check-ups will occur every 6 weeks during the study. Randomization will be via selection of sealed envelope.	Cross-over: Saline Placebo, Then OnabotulinumtoxinA The BA subject group will receive saline and then Onabotulinumtoxin. A.Both groups will then receive OnabotulinumtoxinA in the last two treatments. There will be one treatment at the beginning of each 12 week block, meaning 4 treatments over the 48 week study period total. Progress check-ups will occur every 6 weeks during the study. Randomization will be via selection of sealed envelope.	Open Label Botox Following unblinding, subject elected Botox treatment for 24 week open-label period where all subjects receive Botox treatment.	Open Label Standard of Care Following unblinding, subject elected to a 24-week return to conservative management per standard-of-care protocols.
Open-Label Period Lost to Follow-up	0	0	2	0
Open-Label Period Withdrawal by Subject	0	0	0	1

Baseline Characteristics

Effectiveness of Onabotulinumtoxin A (Botox) in Pediatric Patients Experiencing Migraines: A Study in the Pediatric Pain Population

Baseline characteristics by cohort

Measure	Cross-Over: OnabotulinumtoxinA, Then Saline Placebo n=9 Participants The AB subject group will receive OnabotulinumtoxinA in the first treatment and saline placebo in the second.Both groups will then receive OnabotulinumtoxinA in the last two treatments. There will be one treatment at the beginning of each 12 week block, meaning 4 treatments over the 48 week study period total. Progress check-ups will occur every 6 weeks during the study. Randomization will be via selection of sealed envelope. OnabotulinumtoxinA: The AB subject group will receive OnabotulinumtoxinA in the first treatment and saline placebo in the second.Both groups will then receive OnabotulinumtoxinA in the last two treatments. There will be one treatment at the beginning of each 12 week block, meaning 4 treatments over the 48 week study period total. Progress check-ups will occur every 6 weeks during the study. Randomization will be via selection of sealed envelope. Placebo (Saline): The BA subject group will receive saline and then Onabotulinumtoxin. A.Both groups will then receive OnabotulinumtoxinA in the last two treatments. There will be one treatment at the beginning of each 12 week block, meaning 4 treatments over the 48 week study period total. Progress check-ups will occur every 6 weeks during the study. Randomization will be via selection of sealed envelope.	Cross-Over: Saline Placebo, Then OnabotulinumtoxinA n=6 Participants The BA subject group will receive saline and then Onabotulinumtoxin. A.Both groups will then receive OnabotulinumtoxinA in the last two treatments. There will be one treatment at the beginning of each 12 week block, meaning 4 treatments over the 48 week study period total. Progress check-ups will occur every 6 weeks during the study. Randomization will be via selection of sealed envelope. OnabotulinumtoxinA: The AB subject group will receive OnabotulinumtoxinA in the first treatment and saline placebo in the second.Both groups will then receive OnabotulinumtoxinA in the last two treatments. There will be one treatment at the beginning of each 12 week block, meaning 4 treatments over the 48 week study period total. Progress check-ups will occur every 6 weeks during the study. Randomization will be via selection of sealed envelope. Placebo (Saline): The BA subject group will receive saline and then Onabotulinumtoxin. A.Both groups will then receive OnabotulinumtoxinA in the last two treatments. There will be one treatment at the beginning of each 12 week block, meaning 4 treatments over the 48 week study period total. Progress check-ups will occur every 6 weeks during the study. Randomization will be via selection of sealed envelope.	Total n=15 Participants Total of all reporting groups
Age, Categorical <=18 years	9 Participants n=5 Participants	6 Participants n=7 Participants	15 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (4 weeks) and 12 weeks post each, respective intervention

The frequency of migraines in days.

Outcome measures

Measure	Baseline Period | Control n=15 Participants 4-Week baseline period prior to injection procedures.	Botox Period n=15 Participants 12-Week period where subject receives onabotulinumtoxinA	Placebo Period n=15 Participants 12-week period where subject receives placebo injections.
Frequency of Migraines	28 days Interval 20.0 to 28.0	20 days Interval 7.0 to 28.0	28 days Interval 23.0 to 28.0

PRIMARY outcome

Timeframe: Baseline (4 weeks) and 12 weeks post each, respective intervention

Median intensity of migraines based on 0-10 Pain Numeric Rating Score (NRS). The higher the score, the more intense the pain.

Outcome measures

Measure	Baseline Period | Control n=15 Participants 4-Week baseline period prior to injection procedures.	Botox Period n=15 Participants 12-Week period where subject receives onabotulinumtoxinA	Placebo Period n=15 Participants 12-week period where subject receives placebo injections.
Intensity of Migraines	8 units on a scale Interval 7.0 to 10.0	5 units on a scale Interval 3.0 to 7.0	7 units on a scale Interval 5.0 to 9.0

PRIMARY outcome

Timeframe: Baseline (4 weeks) and 12 weeks post each, respective intervention

Duration of migraines in hours.

Outcome measures

Measure	Baseline Period | Control n=15 Participants 4-Week baseline period prior to injection procedures.	Botox Period n=15 Participants 12-Week period where subject receives onabotulinumtoxinA	Placebo Period n=15 Participants 12-week period where subject receives placebo injections.
Migraine Duration, in Hours	24 hours Interval 13.0 to 24.0	10 hours Interval 2.0 to 24.0	24 hours Interval 4.0 to 24.0

PRIMARY outcome

Timeframe: Baseline (4 weeks) and 12 weeks post each, respective intervention

Pediatric Migraine Disability Score consists of 6 questions: 3 addressing school attendance and functioning, and 3 evaluating participation in events outside of school. The questionnaire is based on the patient's recall of the previous 3 months.

The questionnaire produces a raw score (0-10, 11-30, 31-50, >50) corresponding to a disability grade with increasing severity (little to non, mild, moderate, and severe) which was coded (1, 2, 3, and 4).

Outcome measures

Measure	Baseline Period | Control n=15 Participants 4-Week baseline period prior to injection procedures.	Botox Period n=15 Participants 12-Week period where subject receives onabotulinumtoxinA	Placebo Period n=15 Participants 12-week period where subject receives placebo injections.
Pediatric Migraine Disability Score (PedMIDAS)	4 score on a scale Interval 4.0 to 4.0	3 score on a scale Interval 2.0 to 4.0	4 score on a scale Interval 4.0 to 4.0

SECONDARY outcome

Timeframe: Baseline (4 weeks) and 12 weeks post each, respective intervention

Population: Baseline acted as control so no data for Functionality Improvement collected from participants at baseline.

Improvement of functionality as determined by their Pediatric Migraine Disability Score (PedMIDAS). The PedMIDAS consists of 6 questions: 3 addressing school attendance and functioning, and 3 evaluating participation in events outside of school. The questionnaire is based on the patient's recall of the previous 3 months.

The questionnaire produces a raw score (0-10, 11-30, 31-50, >50) corresponding to a disability grade with increasing severity (little to non, mild, moderate, and severe) which was coded (1, 2, 3, and 4).

Outcome measures

Measure	Baseline Period | Control n=15 Participants 4-Week baseline period prior to injection procedures.	Botox Period n=15 Participants 12-Week period where subject receives onabotulinumtoxinA	Placebo Period 12-week period where subject receives placebo injections.
Functionality Improvement	1 score on a scale Interval 0.0 to 1.0	0 score on a scale Interval -1.0 to 0.0	—

SECONDARY outcome

Timeframe: Baseline (4 weeks) and 12 weeks post each, respective intervention

Subject reported having difficulty sleeping

Outcome measures

Measure	Baseline Period | Control n=15 Participants 4-Week baseline period prior to injection procedures.	Botox Period n=15 Participants 12-Week period where subject receives onabotulinumtoxinA	Placebo Period n=15 Participants 12-week period where subject receives placebo injections.
Difficulty Sleeping	12 Participants	5 Participants	11 Participants

SECONDARY outcome

Timeframe: Baseline (4 weeks) and 12 weeks post each, respective intervention

Admission to hospital

Outcome measures

Measure	Baseline Period | Control n=15 Participants 4-Week baseline period prior to injection procedures.	Botox Period n=15 Participants 12-Week period where subject receives onabotulinumtoxinA	Placebo Period n=15 Participants 12-week period where subject receives placebo injections.
Hospital Admissions	8 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline (4 weeks) and 12 weeks post each, respective intervention

Subject visited an Emergency Department

Outcome measures

Measure	Baseline Period | Control n=15 Participants 4-Week baseline period prior to injection procedures.	Botox Period n=15 Participants 12-Week period where subject receives onabotulinumtoxinA	Placebo Period n=15 Participants 12-week period where subject receives placebo injections.
Emergency Department (ED) Visits	8 Participants	2 Participants	3 Participants

SECONDARY outcome

Timeframe: Baseline (4 weeks) and 12 weeks post, respective intervention

Subject is home schooled full-time.

Outcome measures

Measure	Baseline Period | Control n=15 Participants 4-Week baseline period prior to injection procedures.	Botox Period n=15 Participants 12-Week period where subject receives onabotulinumtoxinA	Placebo Period n=15 Participants 12-week period where subject receives placebo injections.
Home School	2 Participants	2 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline (4 weeks) and 12 weeks post each, respective intervention

Subject is enrolled in a school plan such as IEP, 504 plan, or similar modified school schedule.

Outcome measures

Measure	Baseline Period | Control n=15 Participants 4-Week baseline period prior to injection procedures.	Botox Period n=15 Participants 12-Week period where subject receives onabotulinumtoxinA	Placebo Period n=15 Participants 12-week period where subject receives placebo injections.
School Plan Enrollment	11 Participants	10 Participants	10 Participants

SECONDARY outcome

Timeframe: Baseline (4 weeks) and 12 weeks post each, respective intervention

Population: No data collected from participants at 4-week baseline in order to act as the control.

The duration of benefit in weeks

Outcome measures

Measure	Baseline Period | Control n=15 Participants 4-Week baseline period prior to injection procedures.	Botox Period n=15 Participants 12-Week period where subject receives onabotulinumtoxinA	Placebo Period 12-week period where subject receives placebo injections.
Duration of Benefit	4 weeks Interval 0.0 to 10.0	0 weeks Interval 0.0 to 4.0	—

SECONDARY outcome

Timeframe: Baseline (4 weeks) and 12 weeks post each, respective intervention

Number of concomitant headache medications taken

Outcome measures

Measure	Baseline Period | Control n=15 Participants 4-Week baseline period prior to injection procedures.	Botox Period n=15 Participants 12-Week period where subject receives onabotulinumtoxinA	Placebo Period n=15 Participants 12-week period where subject receives placebo injections.
Concomitant Headache Medications	3 number taken Interval 1.0 to 4.0	1 number taken Interval 0.0 to 4.0	2 number taken Interval 1.0 to 5.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 24-48 weeks post-baseline period

Population: 15 subjects completed the cross-over period. Of those 15, 11 continued Botox (2 lost to follow-up), and 4 elected conservative management (1 discontinued intervention)

The frequency of migraines during the open-label period (2 additional rounds of onabotulinumtoxinA) as compared to the cross-over period.

Outcome measures

Measure	Baseline Period | Control n=4 Participants 4-Week baseline period prior to injection procedures.	Botox Period n=11 Participants 12-Week period where subject receives onabotulinumtoxinA	Placebo Period 12-week period where subject receives placebo injections.
Frequency of Migraines | Open-label Period	28 days Interval 21.0 to 28.0	20 days Interval 5.0 to 28.0	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 24-48 weeks post-baseline period

Population: 15 subjects completed the cross-over period. Of those 15, 11 continued Botox (2 lost to follow-up), and 4 elected conservative management (1 discontinued intervention)

Intensity of migraines during the the open-label period (2 additional rounds of onabotulinumtoxinA) as compared to the cross-over period.

Intensity based on 0-10 Pain Numeric Rating Score (NRS). The higher the score, the more intense the pain.

Outcome measures

Measure	Baseline Period | Control n=15 Participants 4-Week baseline period prior to injection procedures.	Botox Period n=11 Participants 12-Week period where subject receives onabotulinumtoxinA	Placebo Period n=4 Participants 12-week period where subject receives placebo injections.
Intensity of Migraines | Open-Label Period	8 units on a scale Interval 7.0 to 10.0	5 units on a scale Interval 4.0 to 7.0	6 units on a scale Interval 5.0 to 8.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 24-48 weeks post-baseline period

Population: After the unblinding visit, 11 subjects elected to continue with the open-label period and were scheduled to receive two additional rounds of OBTA treatment (2 were lost to follow up). 4 subjects elected to receive standard of care (1 discontinued intervention).

The PedMIDAS the open-label period (2 additional rounds of onabotulinumtoxinA) as compared to the cross-over period.

The PedMIDAS consists of 6 questions: 3 addressing school attendance and functioning, and 3 evaluating participation in events outside of school. The questionnaire is based on the patient's recall of the previous 3 months.

The questionnaire produces a raw score (0-10, 11-30, 31-50, >50) corresponding to a disability grade with increasing severity (little to non, mild, moderate, and severe) which was coded (1, 2, 3, and 4).

Outcome measures

Measure	Baseline Period | Control n=12 Participants 4-Week baseline period prior to injection procedures.	Botox Period n=9 Participants 12-Week period where subject receives onabotulinumtoxinA	Placebo Period n=3 Participants 12-week period where subject receives placebo injections.
Pediatric Migraine Disability Score (PedMIDAS) | Open-Label Period	4 score on a scale Interval 4.0 to 4.0	3 score on a scale Interval 2.0 to 4.0	4 score on a scale Interval 3.0 to 4.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 24-48 weeks post-baseline period

Population: After the unblinding visit, 11 subjects elected to continue with the open-label period and were scheduled to receive two additional rounds of OBTA treatment (2 were lost to follow up). 4 subjects elected to receive standard of care (1 discontinued intervention).

Duration of migraine in hours during the open-label period (2 additional rounds of onabotulinumtoxinA) as compared to the cross-over period.

Outcome measures

Measure	Baseline Period | Control n=12 Participants 4-Week baseline period prior to injection procedures.	Botox Period n=9 Participants 12-Week period where subject receives onabotulinumtoxinA	Placebo Period n=3 Participants 12-week period where subject receives placebo injections.
Duration of Migraine | Open-Label Period	24 hours Interval 13.0 to 24.0	6 hours Interval 2.0 to 14.0	24 hours Interval 24.0 to 24.0

Adverse Events

Cross-over: OnabotulinumtoxinA/Saline Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Cross-over: Saline Placebo/OnabotulinumtoxinA

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Off Label Botox:

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Off Label Standard of Care:

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Shalini Shah, MD

University of California, Irvine | Dept. of Anesthesiology & Perioperative Care

Phone: (949) 824-7246

Email: ssshah1@hs.uci.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place