Trial Outcomes & Findings for L-methylfolate Supplementation to OROS-Methylphenidate Pharmacotherapy in ADHD Adults (NCT NCT01853280)

Last Updated: 2017-11-14

Results Overview

The AISRS is an 18-item questionnaire administered by the clinician assessing each of the individual DSM-IV symptoms of ADHD. Each symptom is rated on a scale of severity from 0 (none) to 3 (severe), and the 18 symptom questions are summed to calculate a total score. The minimum total score is a 0, while the maximum total score is a 54. The AISRS was compared from baseline to completion, over the course of the 12 week study.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

47 participants

Primary outcome timeframe

12 weeks

Results posted on

2017-11-14

Participant Flow

The total enrollment number (those who signed informed consent) was 47, however, 3 subjects were either found ineligible or lost to follow up before they could be assigned to an arm of the study. Thus 44 subjects were randomized to the study.

Participant milestones

Participant milestones
Measure	L-Methylfolate 15 mg of L-Methylfolate (Deplin) daily for 12 weeks as a supplement to OROS-Methylphenidate.	Placebo (for L-Methylfolate) 15 mg matched placebo comparator with open-label OROS-Methylphenidate
Overall Study STARTED	22	22
Overall Study COMPLETED	20	16
Overall Study NOT COMPLETED	2	6

Reasons for withdrawal

Reasons for withdrawal
Measure	L-Methylfolate 15 mg of L-Methylfolate (Deplin) daily for 12 weeks as a supplement to OROS-Methylphenidate.	Placebo (for L-Methylfolate) 15 mg matched placebo comparator with open-label OROS-Methylphenidate
Overall Study Lack of Efficacy	2	2
Overall Study Lost to Follow-up	0	1
Overall Study Physician Decision	0	1
Overall Study Withdrawal by Subject	0	1
Overall Study Ineligible	0	1

Baseline Characteristics

L-methylfolate Supplementation to OROS-Methylphenidate Pharmacotherapy in ADHD Adults

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	L-Methylfolate n=22 Participants 15 mg of L-Methylfolate (Deplin) daily for 12 weeks as a supplement to OROS-Methylphenidate.	Placebo (for L-Methylfolate) n=22 Participants 15 mg matched placebo comparator with open-label OROS-Methylphenidate	Total n=44 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	22 Participants n=5 Participants	22 Participants n=7 Participants	44 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	41.3 years STANDARD_DEVIATION 11.4 • n=5 Participants	37.7 years STANDARD_DEVIATION 8.9 • n=7 Participants	39.96 years STANDARD_DEVIATION 10.14 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	14 Participants n=7 Participants	27 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	8 Participants n=7 Participants	17 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	21 Participants n=5 Participants	19 Participants n=7 Participants	40 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	19 Participants n=5 Participants	17 Participants n=7 Participants	36 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	22 Participants n=5 Participants	22 Participants n=7 Participants	44 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: While 44 subjects were randomized to receive the study drug, only 41 subjects actually began taking the medication, and as such were evaluated using the AISRS.

Outcome measures

Outcome measures
Measure	L-Methylfolate n=22 Participants 15 mg of L-Methylfolate (Deplin) daily for 12 weeks as a supplement to OROS-Methylphenidate.	Placebo (for L-Methylfolate) n=19 Participants 15 mg matched placebo comparator with open-label OROS-Methylphenidate
Adult ADHD Investigator Symptom Rating Scale (AISRS)	-22.9 units on a scale Standard Deviation 10.4	-20.8 units on a scale Standard Deviation 11.3

Adverse Events

L-Methylfolate

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

Placebo (for L-Methylfolate)

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Craig Surman

Massachusetts General Hospital

Phone: 617-726-8422

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	L-Methylfolate n=22 participants at risk 15 mg of L-Methylfolate (Deplin) daily for 12 weeks as a supplement to OROS-Methylphenidate.	Placebo (for L-Methylfolate) n=22 participants at risk 15 mg matched placebo comparator with open-label OROS-Methylphenidate
Nervous system disorders Headache	77.3% 17/22 • Number of events 40 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.	27.3% 6/22 • Number of events 12 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.
Nervous system disorders Insomnia	50.0% 11/22 • Number of events 24 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.	36.4% 8/22 • Number of events 16 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.
Nervous system disorders Sedation	13.6% 3/22 • Number of events 3 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.	13.6% 3/22 • Number of events 3 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.
Infections and infestations Cold/Infection/Allergy	54.5% 12/22 • Number of events 17 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.	27.3% 6/22 • Number of events 11 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.
Musculoskeletal and connective tissue disorders Musculoskeletal	36.4% 8/22 • Number of events 19 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.	31.8% 7/22 • Number of events 8 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.
Gastrointestinal disorders Decreased Appetite	31.8% 7/22 • Number of events 15 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.	45.5% 10/22 • Number of events 29 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.
Nervous system disorders Tense/Jittery	27.3% 6/22 • Number of events 11 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.	13.6% 3/22 • Number of events 3 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.
Gastrointestinal disorders Nausea/Vomit/Diarrhea	27.3% 6/22 • Number of events 18 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.	31.8% 7/22 • Number of events 10 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.
Nervous system disorders Neurological	4.5% 1/22 • Number of events 1 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.	13.6% 3/22 • Number of events 5 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.
General disorders Decreased energy	4.5% 1/22 • Number of events 1 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.	0.00% 0/22 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.
Nervous system disorders Mucosal Dryness	27.3% 6/22 • Number of events 15 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.	45.5% 10/22 • Number of events 25 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.
Psychiatric disorders Anxious/worried	18.2% 4/22 • Number of events 6 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.	13.6% 3/22 • Number of events 5 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.
Psychiatric disorders Agitated/irritable	4.5% 1/22 • Number of events 4 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.	18.2% 4/22 • Number of events 5 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.
Psychiatric disorders Sad/down	13.6% 3/22 • Number of events 5 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.	22.7% 5/22 • Number of events 5 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.
Cardiac disorders Cardiovascular	13.6% 3/22 • Number of events 3 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.	13.6% 3/22 • Number of events 11 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.
Skin and subcutaneous tissue disorders Dermatological	4.5% 1/22 • Number of events 1 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.	13.6% 3/22 • Number of events 3 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.
Reproductive system and breast disorders Genitourinary	4.5% 1/22 • Number of events 1 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.	4.5% 1/22 • Number of events 1 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.
Nervous system disorders Dizzy/lightheaded	0.00% 0/22 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.	13.6% 3/22 • Number of events 3 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.
Nervous system disorders Autonomic: Drool/sweat	0.00% 0/22 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.	9.1% 2/22 • Number of events 5 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.
Nervous system disorders Tics	0.00% 0/22 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.	4.5% 1/22 • Number of events 1 • Adverse event data was collected throughout the entire time subjects were enrolled in the study beginning as their screening visit and ending at their week 12 completion visit.