ADHD
Conditions
Keywords
ADHD, executive function, emotional self-regulation
Brief summary
The investigators are proposing to test a medication derived from our prior studies of the gene SLC9A9. This one gene makes NHE proteins that control how we learn and remember items, which is impaired in ADHD and may cause an inability to plan, prioritize, self-monitor,inhibit, initiate, self-correct, or control one's behavior. The investigators now propose to investigate the therapeutic utility of an NHE inhibitor, amiloride hydrochloride, for the treatment of attention deficit hyperactivity disorder (ADHD) in medication-naïve adults with ADHD.
Detailed description
Our specific aims and hypotheses are as follows: Primary Aim: Assess the efficacy and adverse effects of amiloride in medication naive ADHD adults in a placebo controlled study. Hypothesis 1: Amiloride will reduce scores on our primary outcome measure, the Adult Attention-Deficit/Hyperactivity Disorder Investigator Symptom Rating Scale (AISRS) and on our secondary outcome, the ADHD specific Clinical Global Impressions (CGI) improvement scale. Hypothesis 2: Amiloride will be well tolerated and will have few side effects in adults with ADHD. Exploratory Aim 2: Assess effects of amiloride on ADHD-associated clinical features. We will also assess, in an exploratory manner, the effect of amiloride on two clinical features that are not well treated by current ADHD medications: deficits in emotional self-regulation (DESR) and executive function deficit (EFD). Hypothesis 3 predicts that amiloride treatment will reduce symptoms of DESR and of EFD. We will recruit 40 adults who are diagnosed with ADHD in a double blind placebo controlled study. 20 subjects will receive amiloride hydrochloride and 20 subjects will receive placebo for 8 weeks. Participation in the study requires subjects to meet with the physician for a screening visit, baseline visit and 8 additional weekly visits.
Interventions
DRUGamiloride
Subjects will take either amiloride hydrochloride or placebo for 8 weeks.
BEHAVIORALBehavioral
Each week of the study, subjects will complete the AISRS, BRIEF-A, and CGI to measure symptom improvement
Sponsors
State University of New York - Upstate Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
1. Medication naïve male or female adults ages 18-55 years. 2. A diagnosis of DSM-IV ADHD combined type based on clinical assessment by the study psychiatrist using the Conners Adult ADHD Diagnostic Interview; 3. proficiency in English; 4. A baseline score of 24 or more on the AISRS; 5. ability to swallow pills; 6. ability to report reliably, understand the nature of the study and sign an informed consent document as determined by the study psychiatrist
Exclusion criteria
We will exclude potential participants who: 1. have had pharmacologic treatment for ADHD in the past year; 2. are pregnant or nursing; 3. are Investigators or their immediate family (spouse, parent, child, grandparent, or grandchild); 4. have any serious, unstable medical illness including hepatic, renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease; 5. have severe allergies or multiple adverse drug reactions; 6. have a current or past history of seizures; 7. meet current DSM-IV criteria for anxiety or depression or illicit substance abuse in prior six months (these exclusions are feasible because, although the lifetime comorbidity of ADHD with these disorders is high, we and others have shown that the presence of these disorders at the time of ascertainment for adult ADHD studies is less than 10%); 8. are judged by the study psychiatrist to be at serious suicidal risk. 9. have current or past diagnoses of schizophrenia or bipolar disorder; 10. have a history of hypersensitivity to amiloride or drug class members; 11. have a history of hyperkalemia, diabetes mellitus, renal disease or anuria; 12. have renal impairment Cr \> 1.5; or 13. are taking potassium supplements, aldosterone antagonists, tacrolimus or ACE inhibitors.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Improvement in CGI | 8 weeks | CGI Improvement scale: 1=very much improved; 2=Much improved; 3=Minimally improved; 4=No change; 5=Minimally worse; 6=Much worse; 7=Very much worse |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AISRS, Adult ADHD Investigator Rating Scale | 8 weeks | An 18 item clinician administered questionnaire to evaluate ADHD in adults. Responses to questions were 0-None, 1-Mild, 2-Moderate, 3-Severe. A decrease of 30% in the total score would be considered improvement. Total score range is 0-54. A lower score indicates improvement in symptoms. A score of 24 or more indicates symptomatic ADHD. |
| The Behavior Rating Inventory of Executive Function-Adult (BRIEF-A) | 8 weeks | BRIEF-A is a 75 item self report questionnaire that measures behavior and executive function. For each item the subject is asked during the past month, how often has each of the following behaviors been a problem?: The choices are N (never), S (sometimes), O (Often). Total score for the Global Executive Composite used. Raw data were transformed into t-scores, which are standardized scores that indicate the number of standard deviations away from the mean. A T-score of 50 is equal to the mean. Values less than 65 indicate executive function is not a problem and values greater than 65 indicate executive function is often a problem. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited via a medical clinic and outside advertisement. Due to the stringent inclusion/exclusion criteria, we were only able to recruit 3 subjects and the physician who was conducting the study chose not to continue and we were unable to find another physician.
Participants by arm
| Arm | Count |
|---|---|
| Arm 1-Amiloride Subjects received amiloride hydrochloride (5 mg for 2 weeks, 10 mg for 3 week, and 15 mg for 3 weeks. | 2 |
| Arm 2-Placebo Subjects received placebo for 8 weeks. | 1 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Arm 1-Amiloride | Arm 2-Placebo | 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 | 2 Participants | 1 Participants | 3 Participants |
| CGI | 4.0 units on a scale | 5 units on a scale | 4.33 units on a scale |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 1 Participants | 3 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 1 Participants | 3 Participants |
| Region of Enrollment United States | 2 participants | 1 participants | 3 participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 2 | 0 / 1 |
| serious Total, serious adverse events | 0 / 2 | 0 / 1 |
Outcome results
Primary
Improvement in CGI
CGI Improvement scale: 1=very much improved; 2=Much improved; 3=Minimally improved; 4=No change; 5=Minimally worse; 6=Much worse; 7=Very much worse
Time frame: 8 weeks
Population: There was no statistical analysis done due to the small number of participants in the study
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Amiloride | Improvement in CGI | CGI Week 4 | 4 Units on a scale |
| Amiloride | Improvement in CGI | CGI Week 9 | 3.5 Units on a scale |
| Amiloride | Improvement in CGI | CGI Week 6 | 3.5 Units on a scale |
| Amiloride | Improvement in CGI | CGI Week 10 | 3.5 Units on a scale |
| Amiloride | Improvement in CGI | CGI Week 5 | 4 Units on a scale |
| Amiloride | Improvement in CGI | CGI Week 3 | 4 Units on a scale |
| Amiloride | Improvement in CGI | CGI Week 7 | 4 Units on a scale |
| Amiloride | Improvement in CGI | CGI Week 8 | 3.5 Units on a scale |
| Placebo | Improvement in CGI | CGI Week 8 | 5 Units on a scale |
| Placebo | Improvement in CGI | CGI Week 4 | 3 Units on a scale |
| Placebo | Improvement in CGI | CGI Week 5 | 5 Units on a scale |
| Placebo | Improvement in CGI | CGI Week 6 | 5 Units on a scale |
| Placebo | Improvement in CGI | CGI Week 3 | 5 Units on a scale |
| Placebo | Improvement in CGI | CGI Week 9 | 5 Units on a scale |
| Placebo | Improvement in CGI | CGI Week 10 | 5 Units on a scale |
| Placebo | Improvement in CGI | CGI Week 7 | 5 Units on a scale |
Secondary
AISRS, Adult ADHD Investigator Rating Scale
An 18 item clinician administered questionnaire to evaluate ADHD in adults. Responses to questions were 0-None, 1-Mild, 2-Moderate, 3-Severe. A decrease of 30% in the total score would be considered improvement. Total score range is 0-54. A lower score indicates improvement in symptoms. A score of 24 or more indicates symptomatic ADHD.
Time frame: 8 weeks
Population: Statistical analysis of the outcome data was not done due to the small N.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Amiloride | AISRS, Adult ADHD Investigator Rating Scale | Week 4 | 38.5 Total score |
| Amiloride | AISRS, Adult ADHD Investigator Rating Scale | Week 5 | 32.5 Total score |
| Amiloride | AISRS, Adult ADHD Investigator Rating Scale | Week 6 | 31 Total score |
| Amiloride | AISRS, Adult ADHD Investigator Rating Scale | Week 8 | 34 Total score |
| Amiloride | AISRS, Adult ADHD Investigator Rating Scale | Week 9 | 26 Total score |
| Amiloride | AISRS, Adult ADHD Investigator Rating Scale | Week 10 | 32.5 Total score |
| Amiloride | AISRS, Adult ADHD Investigator Rating Scale | Week 3 | 39 Total score |
| Amiloride | AISRS, Adult ADHD Investigator Rating Scale | Week 7 | 31 Total score |
| Placebo | AISRS, Adult ADHD Investigator Rating Scale | Week 7 | 50 Total score |
| Placebo | AISRS, Adult ADHD Investigator Rating Scale | Week 4 | 51 Total score |
| Placebo | AISRS, Adult ADHD Investigator Rating Scale | Week 9 | 50 Total score |
| Placebo | AISRS, Adult ADHD Investigator Rating Scale | Week 5 | 50 Total score |
| Placebo | AISRS, Adult ADHD Investigator Rating Scale | Week 3 | 54 Total score |
| Placebo | AISRS, Adult ADHD Investigator Rating Scale | Week 6 | 50 Total score |
| Placebo | AISRS, Adult ADHD Investigator Rating Scale | Week 10 | 50 Total score |
| Placebo | AISRS, Adult ADHD Investigator Rating Scale | Week 8 | 50 Total score |
Secondary
The Behavior Rating Inventory of Executive Function-Adult (BRIEF-A)
BRIEF-A is a 75 item self report questionnaire that measures behavior and executive function. For each item the subject is asked during the past month, how often has each of the following behaviors been a problem?: The choices are N (never), S (sometimes), O (Often). Total score for the Global Executive Composite used. Raw data were transformed into t-scores, which are standardized scores that indicate the number of standard deviations away from the mean. A T-score of 50 is equal to the mean. Values less than 65 indicate executive function is not a problem and values greater than 65 indicate executive function is often a problem.
Time frame: 8 weeks
Population: Statistical analysis of the outcome data was not done due to the small N of each group
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Amiloride | The Behavior Rating Inventory of Executive Function-Adult (BRIEF-A) | Week 9 | 62.5 Global Executive Composite T Score |
| Amiloride | The Behavior Rating Inventory of Executive Function-Adult (BRIEF-A) | Week 5 | 68 Global Executive Composite T Score |
| Amiloride | The Behavior Rating Inventory of Executive Function-Adult (BRIEF-A) | Week 6 | 68.5 Global Executive Composite T Score |
| Amiloride | The Behavior Rating Inventory of Executive Function-Adult (BRIEF-A) | Week 10 | 62 Global Executive Composite T Score |
| Amiloride | The Behavior Rating Inventory of Executive Function-Adult (BRIEF-A) | Week 3 | 66.5 Global Executive Composite T Score |
| Amiloride | The Behavior Rating Inventory of Executive Function-Adult (BRIEF-A) | Week 7 | 62.5 Global Executive Composite T Score |
| Amiloride | The Behavior Rating Inventory of Executive Function-Adult (BRIEF-A) | Week 8 | 62.5 Global Executive Composite T Score |
| Amiloride | The Behavior Rating Inventory of Executive Function-Adult (BRIEF-A) | Week 4 | 70.5 Global Executive Composite T Score |
| Placebo | The Behavior Rating Inventory of Executive Function-Adult (BRIEF-A) | Week 7 | 96 Global Executive Composite T Score |
| Placebo | The Behavior Rating Inventory of Executive Function-Adult (BRIEF-A) | Week 4 | 92 Global Executive Composite T Score |
| Placebo | The Behavior Rating Inventory of Executive Function-Adult (BRIEF-A) | Week 3 | 95 Global Executive Composite T Score |
| Placebo | The Behavior Rating Inventory of Executive Function-Adult (BRIEF-A) | Week 5 | 96 Global Executive Composite T Score |
| Placebo | The Behavior Rating Inventory of Executive Function-Adult (BRIEF-A) | Week 6 | 96 Global Executive Composite T Score |
| Placebo | The Behavior Rating Inventory of Executive Function-Adult (BRIEF-A) | Week 9 | 96 Global Executive Composite T Score |
| Placebo | The Behavior Rating Inventory of Executive Function-Adult (BRIEF-A) | Week 8 | 96 Global Executive Composite T Score |
| Placebo | The Behavior Rating Inventory of Executive Function-Adult (BRIEF-A) | Week 10 | 96 Global Executive Composite T Score |