Amiloride Hydrochloride as an Effective Treatment for ADHD

• ClinicalTrials.gov Identifier: NCT01733680
• Recruitment Status: Terminated
• First Posted: November 27, 2012
• Results First Posted: July 20, 2018
• Last Update Posted: July 20, 2018
• Sponsor: State University of New York - Upstate Medical University
• Information provided by (Responsible Party): State University of New York - Upstate Medical University

Tracking Information

• First Submitted Date: November 20, 2012
• First Posted Date: November 27, 2012
• Results First Submitted Date: December 30, 2015
• Results First Posted Date: July 20, 2018
• Last Update Posted Date: July 20, 2018
• Study Start Date: September 2012
• Actual Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 6, 2017)

Improvement in CGI [ Time Frame: 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

Original Primary Outcome Measures (submitted: November 26, 2012)

Improvement in ADHD symptoms [ Time Frame: 8 weeks ]

Improvement in ADHD symptoms measured by the AISRS and the CGI scales.

Current Secondary Outcome Measures (submitted: October 6, 2017)

• AISRS, Adult ADHD Investigator Rating Scale [ Time Frame: 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) [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: November 26, 2012)

Improvement in executive function and emotional self-regulation. [ Time Frame: 8 weeks ]

Measuring improvement in executive function and emotional self-regulation on the Behavior Rating Inventory of Executive Function - Adult Version

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Amiloride Hydrochloride as an Effective Treatment for ADHD
• Official Title: Amiloride Hydrochloride as an Effective Treatment for ADHD
• 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.

• Study Type: Interventional
• Study Phase: Early Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: ADHD

Intervention

• Drug: amiloride
  Subjects will take either amiloride hydrochloride or placebo for 8 weeks.
• Behavioral: Behavioral
  Each week of the study, subjects will complete the AISRS, BRIEF-A, and CGI to measure symptom improvement
  Other Name: ADHD symptoms, executive function, emotional self-regulation

Study Arms

• Active Comparator: Amiloride

  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.

  Interventions:

  • Drug: amiloride
  • Behavioral: Behavioral
• Placebo Comparator: Placebo
  Drug: Subjects will take placebo for 8 weeks Behavioral: Each week subjects will complete questionnaires: AISRS, BRIEF-A, and CGI
  Intervention: Behavioral: Behavioral

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: October 6, 2017): 3
• Original Estimated Enrollment (submitted: November 26, 2012): 40
• Actual Study Completion Date: September 2015
• Actual Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01733680
• Other Study ID Numbers: 320969
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: State University of New York - Upstate Medical University
• Study Sponsor: State University of New York - Upstate Medical University
• Collaborators: Not Provided

Investigators

• Principal Investigator: Stephen V Faraone, PhD; SUNY Upstate Medical Unversity
• Principal Investigator: Prashant Kaul, MD; VA Medical Center at Syracuse

• PRS Account: State University of New York - Upstate Medical University
• Verification Date: October 2017