Clinical trial NCT01733680: Amiloride Hydrochloride as an Effective Treatment for ADHD
Official title: Amiloride Hydrochloride as an Effective Treatment for ADHD
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: EARLY_PHASE1
Conditions: ADHD
Keywords: ADHD
executive function
emotional self-regulation
Lead sponsor: State University of New York - Upstate Medical University
Sponsor class: OTHER
First posted: 2012-11-27
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Improvement in CGI
timeFrame: 8 weeks
Secondary outcomes:
measure: AISRS, Adult ADHD Investigator Rating Scale
timeFrame: 8 weeks
measure: The Behavior Rating Inventory of Executive Function-Adult (BRIEF-A)
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
Study officials:
affiliation: SUNY Upstate Medical Unversity
name: Stephen V Faraone, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: VA Medical Center at Syracuse
name: Prashant Kaul, MD
role: PRINCIPAL_INVESTIGATOR
References: