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The purpose of this pilot study is to compare Adderall ® and Adderall XR ® in terms of their effectiveness and side effects for the treatment of ADHD in adults.
This will be a randomized, cross-over study in which adults with ADHD will receive three weeks of treatment with Adderall (IR) (15, 30, or 45 mg TID) and three weeks of treatment of Adderall XR (XR) (15, 30, or 45 mg QD) for evaluation of dosing adherence and treatment efficacy. The order of the two conditions (TID-QD or QD-TID) will be counterbalanced across subjects, with a washout period in between treatment periods. Participants will be required to come to the site for 9 visits over approximately an 8-week period.
The study will consist of the following four phases:
Phase 1
Phase 2
o Treatment Period "A" - participants will take either Adderall or Adderall XR for 3 weeks (Visits 3-5)
Phase 3
Phase 4 o Treatment Period "B" - participants will take either Adderall or Adderall XR for 3 weeks (Visits 7-9)
Eligible participants will be randomized in a 1:1 ratio to one of two schedules of treatment, Adderall IR followed by Adderall XR, or Adderall XR followed by Adderall IR. Within both schedules, each treatment will consist of a 3-week dose optimization titration evaluation period with a washout week prior to switching to the second respective treatment. The maximum total daily dose will be 45mg, with 15mg TID for IR or 45mg QD for XR. Throughout the medication treatment periods, participants will visit the clinic weekly for evaluations of efficacy, tolerance, and adherence. Medical evaluations will also be conducted at each treatment visit, including assessment of weight, blood pressure, and pulse. Efficacy and adherence data will collected by separate research staff, so that the rater evaluating efficacy will be blinded to the adherence results. The clinician evaluating efficacy will also be blinded to the participants' treatment assignment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Adderall Extended Release First | Experimental | This group was treated with Adderall extended release, either during phase 2 of the trial, or during phase 3 (this subset received Adderall immediate release during phase 2 and then underwent a washout period). This was a counterbalanced crossover study, with a washout period in between treatment periods. Participants were randomized in a 1:1 ratio to one of two schedules Adderall IR followed by Adderall XR, or Adderall XR followed by Adderall IR. |
|
| Adderall Immediate Release First | Experimental | This group was treated with Adderall immediate release, either during phase 2 of the trial, or during phase 3 (this subset received Adderall extended release during phase 2 and then underwent a washout period). This was a counterbalanced crossover study, with a washout period in between treatment periods. Participants were randomized in a 1:1 ratio to one of two schedules Adderall IR followed by Adderall XR, or Adderall XR followed by Adderall IR. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Adderall ® Immediate Release | Drug | Adderall Immediate release (IR) was provided as treatment for three weeks (at 15, 30 or 45 mg TID). The medication was optimized for titration. |
| Measure | Description | Time Frame |
|---|---|---|
| Medication Event Monitoring System (MEMS®) Dosage Adherence | Dosage adherence (MEMSd) is the number of bottle openings divided by number of doses prescribed. Adherence was measured as ≥ 75% of the doses. The number below is the total percentage of subjects who were adherent. | The MEMS information was noted at clinic visit 3, 4, 5, 7, 8, and 9 (over 8 weeks) |
| Medication Event Monitoring System (MEMS®) Regimen Adherence | Regimen adherence (MEMSr) is a percentage of the number of days in which the complete dose regimen was taken as prescribed. Adherence was measured as complete dose regimen taken on ≥ 90% of days. The number below is the total percentage of subjects who were adherent. | The MEMS information was noted at clinic visit 3, 4, 5, 7, 8, and 9 (over 8 weeks) |
| Medication Event Monitoring System (MEMS®) Time Adherence | Time adherence (MEMSt) is the percentage of doses taken as prescribed within a specified time period. Adherence was measured as ≥ 80% of doses taken at the correct time. The number below is the percentage of subjects who were adherent. | The MEMS information was noted at clinic visit 3, 4, 5, 7, 8, and 9 (over 8 weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| Pill Count | Study staff counted unused medication at each weekly visit to yield a percentage of prescribed pills that were consumed. For each group, the number given will be the total number of consumed pills divided by total number of pill prescribed. | At clinic visit 3, 4, 5, 7, 8, and 9 (over 8 weeks) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Lenard Adler, MD | NYU School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| VANYHHS | New York | New York | 10010 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21904088 | Derived | Adler LA, Lynch LR, Shaw DM, Wallace SP, Ciranni MA, Briggie AM, Kulaga A, O'Donnell KE, Faraone SV. Medication adherence and symptom reduction in adults treated with mixed amphetamine salts in a randomized crossover study. Postgrad Med. 2011 Sep;123(5):71-9. doi: 10.3810/pgm.2011.09.2461. |
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Individuals who were currently receiving amphetamine or methylphenidate treatment underwent a 7-day washout period before the baseline visit; those receiving atomoxetine or other medications for ADHD were required to undergo a 28-day washout period before the baseline visit. While 62 subjects started the study, only 49 finished the full study.
Men or women, aged 18 to 55 years, who met the DSM-IV criteria for ADHD, as assessed by the Adult ADHD Clinician Diagnostic Scale (ACDS) version 1.2, were eligible to participate. Participants were recruited from local advertising or from the pool of participants at the MHADRP at NYU School of Medicine and VA NY Harbor Healthcare System.
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| ID | Title | Description |
|---|---|---|
| FG000 | Extended Release First | This group received the extended release medication during the first three weeks of treatment and then received the immediate release medication during the last 3 weeks of treatment. |
| FG001 | Immediate Release First | This group received the immediate release medication during the first three weeks of treatment and then received the extended release medication during the last 3 weeks of treatment. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention (3 Weeks) |
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| Second Intervention (3 Weeks) |
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| ID | Title | Description |
|---|---|---|
| BG000 | All Participants | This was a randomized, crossover study in which participants received 3 weeks of treatment with MAS IR (15, 30, or 45 mg TID) and 3 weeks of treatment with MAS XR (15, 30, or 45 mg qAM). The order of the treatments (TID-qAM or qAM-TID) was counterbalanced across participants, with a washout period of ≥ 7 days between epochs. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Medication Event Monitoring System (MEMS®) Dosage Adherence | Dosage adherence (MEMSd) is the number of bottle openings divided by number of doses prescribed. Adherence was measured as ≥ 75% of the doses. The number below is the total percentage of subjects who were adherent. | These is the total of participants who completed the study. | Posted | Number | percentage of participants adherent | The MEMS information was noted at clinic visit 3, 4, 5, 7, 8, and 9 (over 8 weeks) |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Extended Release | This was a randomized, crossover study in which participants received 3 weeks of treatment with MAS IR (15, 30, or 45 mg TID) and 3 weeks of treatment with MAS XR (15, 30, or 45 mg qAM). The order of the treatments (TID-qAM or qAM-TID) was counterbalanced across participants, with a washout period of ≥ 7 days between epochs. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Vascular disorders |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Lenard Adler | NYU School of Medicine | (212) 263-3580 | lenard.adler@nyumc.org |
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| ID | Term |
|---|---|
| D001289 | Attention Deficit Disorder with Hyperactivity |
| ID | Term |
|---|---|
| D019958 | Attention Deficit and Disruptive Behavior Disorders |
| D065886 | Neurodevelopmental Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| C090411 | Adderall |
| C449521 | SLI381 |
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| Adderall XR ® | Drug | Adderall Extended Release (XR) was provided as treatment for three weeks at (15, 30, or 45 mg QD). The medication was optimized for titration. |
|
|
| Self Report |
Self-reported adherence was ascertained via retrospective self-report of daily regimen adherence. Participants were considered adherent for Adderall IR (Methamphetamine salts) if they took the first does in the morning within 30 minutes of waking, and then each subsequent dose in 5-hour intervals (within 30 minutes). For Adderall XR (Methamphetamine salts), participants were considered adherent if they took the single daily dose in the morning within 30 minutes of waking. The number given below represents the total number of self-reported adherent participants divided by the total number of participants per group, times 100 (to obtain percentage). |
| At clinic visit 3, 4, 5, 7, 8, and 9 (over 8 weeks) |
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| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | Participants |
|
| OG001 | Adderall XR (Methamphetamine Salts) | All participants were initiated at a total daily dose of 15 mg/day (15 mg qAM for Adderall XR (Methamphetamine Salts)). At visits 3 and 4, the total daily dose of MAS was increased by 15 mg/day until an optimal dose or the maximum total daily dose of 45 mg/day was reached. An optimal dose was determined by clinical efficacy (a ≥ 30% reduction in the baseline total ADHD Rating Scale [ADHD-RS] scores) and tolerability. |
|
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| Primary | Medication Event Monitoring System (MEMS®) Regimen Adherence | Regimen adherence (MEMSr) is a percentage of the number of days in which the complete dose regimen was taken as prescribed. Adherence was measured as complete dose regimen taken on ≥ 90% of days. The number below is the total percentage of subjects who were adherent. | Posted | Number | percentage of participants adherent | The MEMS information was noted at clinic visit 3, 4, 5, 7, 8, and 9 (over 8 weeks) |
|
|
|
| Primary | Medication Event Monitoring System (MEMS®) Time Adherence | Time adherence (MEMSt) is the percentage of doses taken as prescribed within a specified time period. Adherence was measured as ≥ 80% of doses taken at the correct time. The number below is the percentage of subjects who were adherent. | Posted | Number | percentage of participants adherent | The MEMS information was noted at clinic visit 3, 4, 5, 7, 8, and 9 (over 8 weeks) |
|
|
|
| Secondary | Pill Count | Study staff counted unused medication at each weekly visit to yield a percentage of prescribed pills that were consumed. For each group, the number given will be the total number of consumed pills divided by total number of pill prescribed. | Posted | Number | percentage of pills consumed | At clinic visit 3, 4, 5, 7, 8, and 9 (over 8 weeks) |
|
|
|
| Secondary | Self Report | Self-reported adherence was ascertained via retrospective self-report of daily regimen adherence. Participants were considered adherent for Adderall IR (Methamphetamine salts) if they took the first does in the morning within 30 minutes of waking, and then each subsequent dose in 5-hour intervals (within 30 minutes). For Adderall XR (Methamphetamine salts), participants were considered adherent if they took the single daily dose in the morning within 30 minutes of waking. The number given below represents the total number of self-reported adherent participants divided by the total number of participants per group, times 100 (to obtain percentage). | Posted | Number | percentage of participants adherent | At clinic visit 3, 4, 5, 7, 8, and 9 (over 8 weeks) |
|
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|
| 0 |
| 62 |
| 53 |
| 62 |
| EG001 | Immediate Release | This was a randomized, crossover study in which participants received 3 weeks of treatment with MAS IR (15, 30, or 45 mg TID) and 3 weeks of treatment with MAS XR (15, 30, or 45 mg qAM). The order of the treatments (TID-qAM or qAM-TID) was counterbalanced across participants, with a washout period of ≥ 7 days between epochs. | 0 | 62 | 53 | 62 |
| Insomnia | General disorders |
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| Loss of Appetite/Anorexia | General disorders |
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| Anxiety | Psychiatric disorders |
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| Trismus | Musculoskeletal and connective tissue disorders |
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| Feeling Speedy or Wired or Jittery | Psychiatric disorders |
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| Nausea | Gastrointestinal disorders |
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| Dry Mouth | General disorders |
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