Attention Deficit Hyperactivity Disorder
Conditions
Keywords
ADHD, Attention Deficit Hyperactivity Disorder, Deplin, L-methylfolate, Natural Treatments, Medical Food
Brief summary
This pilot study seeks to evaluate initial evidence for the effect of L-methylfolate supplementation to OROS-Methylphenidate pharmacotherapy on ADHD symptoms and associated features in adults with ADHD, as well as tolerability of this supplementation. The investigators will conduct a 12-week double-blind randomized placebo-controlled trial with L-methylfolate supplementing open-label OROS-Methylphenidate (OROS-MPH). The investigators propose to examine 40 adult (ages 18-55) subjects satisfying the DSM-IV diagnostic criteria for ADHD.
Interventions
DRUGL-methylfolate
15mg/day L-methylfolate.
All subjects will be treated with open-label OROS-MPH
DRUGPlacebo
15 mg matched placebo comparator, with open-label OROS-Methylphenidate
Sponsors
Pamlab, Inc.
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female adults ages 18-55 years of age. 2. A diagnosis of childhood onset ADHD, meeting all but the age of onset criteria according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), based on clinical assessment. Childhood onset will be defined according to established research criteria, requiring onset of two symptoms of inattentive or of impulsive/hyperactive traits by the age of 12. 3. A score of 24 or more on the Adult ADHD Investigator Symptom Report Scale (AISRS).
Exclusion criteria
1. A history of non-response or intolerance to methylphenidate at adequate doses as determined by the clinician. 2. A history of intolerance to L-methylfolate supplementation. 3. Pregnant or nursing females. 4. Serious, unstable medical illness including hepatic, renal, gastroenterological, respiratory, cardiovascular, endocrinologic (thyroid), neurologic (seizure), immunologic, or hematologic disease. 5. Glaucoma. 6. Clinically unstable psychiatric conditions including suicidality, homicidality, bipolar disorder, psychosis, history of or current marked anxiety, tension or agitation potentially exacerbated by a stimulant, or lifetime history of any other clinically serious condition potentially exacerbated by a stimulant, such as mania or psychosis. 7. Significant impairment due to tics, based on clinician judgment. 8. A family history or diagnosis of Tourette's syndrome 9. Current (within 3 months) DSM-IV criteria for abuse or dependence with any psychoactive substance other than nicotine. 10. Multiple adverse drug reactions. 11. Any other concomitant medication considered to be effective for management of ADHD; individuals on stable treatment with agents with central nervous system activity will be allowed to participate, as detailed in the Concomitant Medication portion of the protocol. 12. Current use of MAO Inhibitor or use within the past two weeks. 13. Investigator and his/her immediate family; defined as the investigator's spouse, parent, child, grandparent, or grandchild. 14. Use of supplemental folic acid greater than 400 mcg per day, L-methylfolate, or Omega-3 Fatty Acids greater than 800 mg per day within two weeks prior to the baseline study visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adult ADHD Investigator Symptom Rating Scale (AISRS) | 12 weeks | 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. |
Countries
United States
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| L-Methylfolate 15 mg of L-Methylfolate (Deplin) daily for 12 weeks as a supplement to OROS-Methylphenidate. | 22 |
| Placebo (for L-Methylfolate) 15 mg matched placebo comparator with open-label OROS-Methylphenidate | 22 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Ineligible | 0 | 1 |
| 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 |
Baseline characteristics
| Characteristic | L-Methylfolate | Placebo (for L-Methylfolate) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants | 22 Participants | 44 Participants |
| Age, Continuous | 41.3 years STANDARD_DEVIATION 11.4 | 37.7 years STANDARD_DEVIATION 8.9 | 39.96 years STANDARD_DEVIATION 10.14 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 19 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 19 Participants | 17 Participants | 36 Participants |
| Region of Enrollment United States | 22 Participants | 22 Participants | 44 Participants |
| Sex: Female, Male Female | 13 Participants | 14 Participants | 27 Participants |
| Sex: Female, Male Male | 9 Participants | 8 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 22 |
| other Total, other adverse events | 20 / 22 | 19 / 22 |
| serious Total, serious adverse events | 0 / 22 | 0 / 22 |
Outcome results
Primary
Adult ADHD Investigator Symptom Rating Scale (AISRS)
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| L-Methylfolate | Adult ADHD Investigator Symptom Rating Scale (AISRS) | -22.9 units on a scale | Standard Deviation 10.4 |
| Placebo (for L-Methylfolate) | Adult ADHD Investigator Symptom Rating Scale (AISRS) | -20.8 units on a scale | Standard Deviation 11.3 |