Amiloride Hydrochloride as an Effective Treatment for ADHD
Primary Purpose
ADHD
Status
Terminated
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
amiloride
Behavioral
Sponsored by
About this trial
This is an interventional treatment trial for ADHD focused on measuring ADHD, executive function, emotional self-regulation
Eligibility Criteria
Inclusion Criteria:
- Medication naïve male or female adults ages 18-55 years.
- A diagnosis of DSM-IV ADHD combined type based on clinical assessment by the study psychiatrist using the Conners Adult ADHD Diagnostic Interview;
- proficiency in English;
- A baseline score of 24 or more on the AISRS;
- ability to swallow pills;
- 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:
- have had pharmacologic treatment for ADHD in the past year;
- are pregnant or nursing;
- are Investigators or their immediate family (spouse, parent, child, grandparent, or grandchild);
- have any serious, unstable medical illness including hepatic, renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease;
- have severe allergies or multiple adverse drug reactions;
- have a current or past history of seizures;
- 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%);
- are judged by the study psychiatrist to be at serious suicidal risk.
- have current or past diagnoses of schizophrenia or bipolar disorder;
- have a history of hypersensitivity to amiloride or drug class members;
- have a history of hyperkalemia, diabetes mellitus, renal disease or anuria;
- have renal impairment Cr > 1.5; or
- are taking potassium supplements, aldosterone antagonists, tacrolimus or ACE inhibitors.
Sites / Locations
- SUNY Upstate Medical University
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Amiloride
Placebo
Arm Description
Drug: Subjects will take 5mg qd Amiloride for 2 weeks, 10mg qd Amiloride for 3 weeks, 15 mg qd Amiloride for 3 weeks. Behavioral: Each week subjects will complete the AISRS, BRIEF-A, and CGI.
Drug: Subjects will take placebo for 8 weeks Behavioral: Each week subjects will complete questionnaires: AISRS, BRIEF-A, and CGI
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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.
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.
Full Information
NCT ID
NCT01733680
First Posted
November 20, 2012
Last Updated
October 6, 2017
Sponsor
State University of New York - Upstate Medical University
1. Study Identification
Unique Protocol Identification Number
NCT01733680
Brief Title
Amiloride Hydrochloride as an Effective Treatment for ADHD
Official Title
Amiloride Hydrochloride as an Effective Treatment for ADHD
Study Type
Interventional
2. Study Status
Record Verification Date
October 2017
Overall Recruitment Status
Terminated
Why Stopped
Study stopped due to lack of recruitment
Study Start Date
September 2012 (undefined)
Primary Completion Date
September 2015 (Actual)
Study Completion Date
September 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
State University of New York - Upstate Medical University
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ADHD
Keywords
ADHD, executive function, emotional self-regulation
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
3 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Amiloride
Arm Type
Active Comparator
Arm Description
Drug: Subjects will take 5mg qd Amiloride for 2 weeks, 10mg qd Amiloride for 3 weeks, 15 mg qd Amiloride for 3 weeks.
Behavioral: Each week subjects will complete the AISRS, BRIEF-A, and CGI.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Drug: Subjects will take placebo for 8 weeks Behavioral: Each week subjects will complete questionnaires: AISRS, BRIEF-A, and CGI
Intervention Type
Drug
Intervention Name(s)
amiloride
Intervention Description
Subjects will take either amiloride hydrochloride or placebo for 8 weeks.
Intervention Type
Behavioral
Intervention Name(s)
Behavioral
Other Intervention Name(s)
ADHD symptoms, executive function, emotional self-regulation
Intervention Description
Each week of the study, subjects will complete the AISRS, BRIEF-A, and CGI to measure symptom improvement
Primary Outcome Measure Information:
Title
Improvement in CGI
Description
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
Secondary Outcome Measure Information:
Title
AISRS, Adult ADHD Investigator Rating Scale
Description
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
Title
The Behavior Rating Inventory of Executive Function-Adult (BRIEF-A)
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Medication naïve male or female adults ages 18-55 years.
A diagnosis of DSM-IV ADHD combined type based on clinical assessment by the study psychiatrist using the Conners Adult ADHD Diagnostic Interview;
proficiency in English;
A baseline score of 24 or more on the AISRS;
ability to swallow pills;
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:
have had pharmacologic treatment for ADHD in the past year;
are pregnant or nursing;
are Investigators or their immediate family (spouse, parent, child, grandparent, or grandchild);
have any serious, unstable medical illness including hepatic, renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease;
have severe allergies or multiple adverse drug reactions;
have a current or past history of seizures;
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%);
are judged by the study psychiatrist to be at serious suicidal risk.
have current or past diagnoses of schizophrenia or bipolar disorder;
have a history of hypersensitivity to amiloride or drug class members;
have a history of hyperkalemia, diabetes mellitus, renal disease or anuria;
have renal impairment Cr > 1.5; or
are taking potassium supplements, aldosterone antagonists, tacrolimus or ACE inhibitors.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephen V Faraone, PhD
Organizational Affiliation
SUNY Upstate Medical Unversity
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Prashant Kaul, MD
Organizational Affiliation
VA Medical Center at Syracuse
Official's Role
Principal Investigator
Facility Information:
Facility Name
SUNY Upstate Medical University
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
12. IPD Sharing Statement
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Amiloride Hydrochloride as an Effective Treatment for ADHD
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