Single-dose Potassium Supplementation in Patients With ADHD for Whom the Anesthetic Lidocaine is Ineffective

Study Overview
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Brief Summary
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Randomized, controlled, double-blind trial of the effect of a single dose of potassium on ADHD symptoms as measured by changes in measures of symptoms of ADHD correlated with the results of their Lidocaine Effectiveness Test.

Detailed Description
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Subjects with a confirmed diagnosis of Attention Deficit Hyperactivity Disorder (ADHD), who are either untreated or poorly controlled with existing ADHD therapy, will be recruited for a single, four-hour session. Each subject will be tested for lidocaine effectiveness using the application of lidocaine gel to the tongue and assessment by taste. The subjects will then be assigned to two arms, (1) lidocaine sensitive (effective) or (2) lidocaine insensitive (ineffective), and then randomized as to an intervention of potassium supplementation or a placebo. Each subject will: Complete questionnaires about their history of certain symptoms and a food diary. Get an ECG to exclude those with arrhythmias. Have their baseline serum potassium tested Have measures of ADHD symptoms performed. Then each subject will receive the intervention of a single dose of the potassium or placebo. After the wait of one hour, a repeat serum potassium and measurement of symptoms will be performed. Note; The FDA also requires a Columbia Suicide Severity Rating Scale (C-SSRS) for all ADHD trials

Official Title
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Single-dose Potassium Supplementation in ADHD Patients With Lidocaine Ineffectiveness

Conditions
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ADHD

Intervention / Treatment
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* Drug: Potassium Gluconate Oral Capsule
* Drug: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previously documented ADHD diagnosis Untreated or taking existing ADHD drugs, but symptoms poorly controlled (e.g., symptoms not well managed by amphetamines, including ongoing inattention and impulsivity) Exclusion Criteria: Well treated with existing ADHD medication Epilepsy IQ less than 80 Severe head trauma that led to loss of consciousness for more than an hour or required surgery Birth weight below 5 pounds or 2270 grams Severe autism (milder conditions described as Asperger syndrome or high-functioning autism are not excluded) Comorbid psychiatric disorders, such as generalized anxiety disorder, major depressive disorder, schizophrenia and schizoaffective disorder, bipolar disorder, and any co-morbid condition at the discretion of the PI that would interfere with a patient's ability to participate Mouth lesions, known to temporarily interfere with lidocaine effectiveness Renal disease or abnormal kidney function or receiving dialysis An individual has a factor likely to reduce penetrance, including excessive salt loss, such as caked salt on the body after exercise and Cystic fibrosis in a relative suggestive of the individual being a carrier. Heart arrhythmia, known or evident on ECG Known intolerance or allergy to lidocaine Already taking supplemental potassium or renin angiotensin aldosterone inhibitors or other potassium elevating agents (see list below) Angiotensin Converting Enzyme Inhibitors Alacepril (not available in US) Benazepril (Lotensin) Captopril (trade name Capoten) Cilazapril (Inhibace) Delapril (not available in US) Enalapril (Vasotec/Renitec) Fosinopril (Fositen/Monopril) Imidapril (Tanatril) Lisinopril (Listril/Lopril/Novatec/Prinivil/Zestril) Moexipril (Univasc) Perindopril (Coversyl/Aceon/Perindo) Quinapril (Accupril) Ramipril (Altace/Prilace/Ramace/Ramiwin/Triatec/Tritace) Spirapril (Renormax) Temocapril (not available in US) Teprotide (but not active by oral administration and not used in US) Trandolapril (Mavik/Odrik/Gopten) Zofenopril Angiotensin receptor blockers Azilsartan (Edarbi) Candesartan (Atacand) Eprosartan (Teveten) Fimasartan (Kanarb) Irbesartan (Avapro) Losartan (Cozaar) Olmesartan (Benicar/Olmetec) Telmisartan (Micardis) Valsartan (Diovan) Aldosterone antagonists Spironolactone (Aldactone) Eplerenone (Inspra) Renin inhibitors a. Aliskiren (Tekturna, Rasilez) Other potassium elevating agents Antibiotics, including penicillin G and trimethoprim Azole antifungals Beta-blockers Herbal supplements, including milkweed, lily of the valley, Siberian ginseng, Hawthorn berries Heparin Nonsteroidal anti-inflammatory medications (NSAIDs) Oral contraceptives containing drospirenone

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The trial will have 2 arms, lidocaine sensitive (effective) and lidocaine insensitive (ineffective). The sample will be enriched to have 50% in each arm. Within each arm, subjects will be randomized on a 1-to-1 allocation to the treatment or control groups. The investigators will adopt an iterative approach of testing of batches of subjects because (1) the frequency of lidocaine-insensitivity is only known approximately, (2) the frequency may be unevenly distributed across ethnic groups, and (3) the exact effect size of the potassium is not known, though reported to be high in off-label use in clinical settings with more chronic administration. At the end of testing 40 patients, the results will be analyzed for statistical significance. (1) If the results are statistically significant with a 95% confidence, the testing may stop with the first batch of 40 subjects. (2) If not, sequential, iterative batches of 20 subjects will be tested, and the results reanalyzed.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lidocaine-effective ADHD: Intervention<br>Single-dose potassium gluconate oral capsule intervention for ADHD subjects for whom lidocaine is effective | Drug: Potassium Gluconate Oral Capsule<br>* Each subject will receive a dose of  8 mg/kg of potassium. We will be giving a maximum of 14 mEq in a single dose.<br>|
| Placebo Comparator: Lidocaine-effective ADHD: Placebo<br>Single-dose placebo oral capsule intervention for ADHD subjects for whom lidocaine is effective | Drug: Placebo oral capsule<br>* Each subject will receive a dose of  8 mg/kg of a placebo capsule<br>|
| Active Comparator: Lidocaine-ineffective ADHD: Intervention<br>Single-dose potassium gluconate oral capsule intervention for ADHD subjects for whom lidocaine is ineffective | Drug: Potassium Gluconate Oral Capsule<br>* Each subject will receive a dose of  8 mg/kg of potassium. We will be giving a maximum of 14 mEq in a single dose.<br>|
| Placebo Comparator: Lidocaine-ineffective ADHD: placebo<br>Single-dose placebo oral capsule intervention for ADHD subjects for whom lidocaine is ineffective | Drug: Placebo oral capsule<br>* Each subject will receive a dose of  8 mg/kg of a placebo capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of lidocaine ineffectiveness in those with ADHD | Investigator assesses identification and intensity of tastes (such as sweet) before and after application of oral lidocaine gel to the tongue. | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | Investigator documentation of adverse reactions to either lidocaine or potassium | 1-2 hours after intervention | 
| Other discomforts | Investigator documentation of complaints or minor discomforts | 1-2 hours after intervention | 
| Change in ADHD-RS questionnaires | The questionnaire is a standard assessment tool for measuring the level of ADHD symptoms. The ADHD-RS-IV is for adults and the ADHD-RSM-5 is for teenagers. This test has been validated for measuring the impact of drugs in ADHD, typically multi-dose, multi-week changes. Since this study is a single-dose, several-hour study, the Investigators will complete only the portions designed to done with the patient and by the clinician; sections designed to be completed by parents and teachers. The results will establish expectations for future multi-dose studies. All scores on a range of None, Mild, Moderate, Severe. Carelessness Difficulty sustaining attention in activities No follow through Can't organize Avoids/dislikes tasks requiring sustained mental effort Loses Important items Easily distractible Forgetful in daily activities | Baseline and  1-2 hours later, 1 hour after intervention | 
| Change in Clinical Global Impression Physician Completed Questionnaire | Clinician-assessed improvement in overall symptoms, using CGI S (severity) as baseline and CGI I (improvement) to track any change. Investigator assesses Compared to his or her condition at baseline, how much has he or she changed? Very much improved Much improved Minimally improved No change Minimally worse Much worse Very much worse | Baseline and  1-2 hours later, 1 hour after intervention | 
| Change in scores using Quotient ADHD System | The Quotient device (http://www.quotient-adhd.com) tracks scores on 6 factors of motion analysis; 6 factors of attention response; and 8 factors of attention state. The subject plays a diagnostic video game and the machine tracks movement of the head, and speed and accuracy of the mouse clicks. The first assessment will serve as a baseline and the assessment post-intervention will measure any changes. (all scores from 0-100) Motion Analysis (including Immobility Duration, Number of movements, displacement, area, spacial complexity, temporal scaling) Attention Response Analysis (including adjusted Accuracy, Omission Errors, Commission Errors, Latency, Variability, Coefficient of Variation for response latency) Attention State Analysis (including number of shifts, Attentive, Impulsive, Distracted, Disengaged, Random, Minimal, Contrary, Overall Results) | Baseline and  1 hour after intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Conditions in which lidocaine is ineffective