Amiloride Hydrochloride as an Effective Treatment for ADHD

• Sponsor: State University of New York - Upstate Medical University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01733680
• Collaborator: (none)
• Enrollment: 3
• Location: 1
• Arms: 2
• Duration (Months): 36
• Patients Per Site Per Month: 0.1

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
ADHD	Drug: amiloride; Behavioral: Behavioral	Early Phase 1

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 Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Amiloride Hydrochloride as an Effective Treatment for ADHD
• Study Start Date: Sep 1, 2012
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
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.	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 Names: ADHD symptoms, executive function, emotional self-regulation
Placebo Comparator: Placebo Drug: Subjects will take placebo for 8 weeks Behavioral: Each week subjects will complete questionnaires: AISRS, BRIEF-A, and CGI	Behavioral: Behavioral; Each week of the study, subjects will complete the AISRS, BRIEF-A, and CGI to measure symptom improvement; Other Names: ADHD symptoms, executive function, emotional self-regulation

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	SUNY Upstate Medical University	Syracuse	New York	United States	13210

Sponsors and Collaborators

• State University of New York - Upstate Medical University

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: State University of New York - Upstate Medical University
• ClinicalTrials.gov Identifier: NCT01733680
• Other Study ID Numbers: 320969
• First Posted: Nov 27, 2012
• Last Update Posted: Jul 20, 2018
• Last Verified: Oct 1, 2017

• Keywords provided by State University of New York - Upstate Medical University: ADHD; executive function; emotional self-regulation
• Additional relevant MeSH terms: Amiloride

Study Results

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.

Arm/Group Title	Amiloride	Placebo
Arm/Group 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. amiloride: Subjects will take either amiloride hydrochloride or placebo for 8 weeks. Behavioral: Each week of the study, subjects will complete the AISRS, BRIEF-A, and CGI to measure symptom improvement	Drug: Subjects will take placebo for 8 weeks Behavioral: Each week subjects will complete questionnaires: AISRS, BRIEF-A, and CGI Behavioral: Each week of the study, subjects will complete the AISRS, BRIEF-A, and CGI to measure symptom improvement
Period Title: Overall Study
STARTED	2	1
COMPLETED	2	0
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Arm 1-Amiloride	Arm 2-Placebo	Total
Arm/Group Description	Subjects received amiloride hydrochloride (5 mg for 2 weeks, 10 mg for 3 week, and 15 mg for 3 weeks.	Subjects received placebo for 8 weeks.	Total of all reporting groups
Overall Participants	2	1	3
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	2 100%	1 100%	3 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	1 50%	0 0%	1 33.3%
Male	1 50%	1 100%	2 66.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	2 100%	1 100%	3 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	2 100%	1 100%	3 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	2 100%	1 100%	3 100%
CGI (units on a scale) [Mean (Full Range) ]
Mean (Full Range) [units on a scale]	4.0	5	4.33

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

There was no statistical analysis done due to the small number of participants in the study

Arm/Group Title	Amiloride	Placebo
Arm/Group 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. amiloride: Subjects will take either amiloride hydrochloride or placebo for 8 weeks. Behavioral: Each week of the study, subjects will complete the AISRS, BRIEF-A, and CGI to measure symptom improvement	Drug: Subjects will take placebo for 8 weeks Behavioral: Each week subjects will complete questionnaires: AISRS, BRIEF-A, and CGI Behavioral: Each week of the study, subjects will complete the AISRS, BRIEF-A, and CGI to measure symptom improvement
Measure Participants	2	1
CGI Week 3	4	5
CGI Week 4	4	3
CGI Week 5	4	5
CGI Week 6	3.5	5
CGI Week 7	4	5
CGI Week 8	3.5	5
CGI Week 9	3.5	5
CGI Week 10	3.5	5

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Statistical analysis of the outcome data was not done due to the small N.

Arm/Group Title	Arm 1-Amiloride	Arm 2-Placebo
Arm/Group Description	Amiloride was administered for 8 weeks. 5 mg for 2 weeks, 10 mg for 3 weeks and 15 mg for 3 weeks	Subjects were given placebo for 8 weeks
Measure Participants	2	1
Week 3	39	54
Week 4	38.5	51
Week 5	32.5	50
Week 6	31	50
Week 7	31	50
Week 8	34	50
Week 9	26	50
Week 10	32.5	50

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Statistical analysis of the outcome data was not done due to the small N of each group

Arm/Group Title	Arm 1-Amiloride	Arm 2-Placebo
Arm/Group Description	Subjects received amiloride hydrochloride for 8 weeks. 5 mg/day for 2 weeks, 10 mg/day for 3 weeks, and 15 mg/day for 3 weeks.	Subjects received placebo for 8 weeks
Measure Participants	2	1
Week 3	66.5	95
Week 4	70.5	92
Week 5	68	96
Week 6	68.5	96
Week 7	62.5	96
Week 8	62.5	96
Week 9	62.5	96
Week 10	62	96

Adverse Events

Time Frame	10 weeks
Adverse Event Reporting Description	Adverse events that were monitored was blood pressure, weight, heart rate, EKG, CBC, TSH, lipid profile, BMP, general malaise, tiredness, headache.
Arm/Group Title	Amiloride		Placebo
Arm/Group 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. amiloride: Subjects will take either amiloride hydrochloride or placebo for 8 weeks. Behavioral: Each week of the study, subjects will complete the AISRS, BRIEF-A, and CGI to measure symptom improvement		Drug: Subjects will take placebo for 8 weeks Behavioral: Each week subjects will complete questionnaires: AISRS, BRIEF-A, and CGI Behavioral: Each week of the study, subjects will complete the AISRS, BRIEF-A, and CGI to measure symptom improvement
All Cause Mortality
	Amiloride		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Amiloride		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	Amiloride		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/1 (0%)

Limitations/Caveats

Because of the low number of subjects enrolled in the study, no outcome measures were statistically analyzed.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.