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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.
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:
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lidocaine-effective ADHD: Intervention | Active Comparator | Single-dose potassium gluconate oral capsule intervention for ADHD subjects for whom lidocaine is effective |
|
| Lidocaine-effective ADHD: Placebo | Placebo Comparator | Single-dose placebo oral capsule intervention for ADHD subjects for whom lidocaine is effective |
|
| Lidocaine-ineffective ADHD: Intervention | Active Comparator | Single-dose potassium gluconate oral capsule intervention for ADHD subjects for whom lidocaine is ineffective |
|
| Lidocaine-ineffective ADHD: placebo | Placebo Comparator | Single-dose placebo oral capsule intervention for ADHD subjects for whom lidocaine is ineffective |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Potassium Gluconate Oral Capsule | Drug | 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. |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
Angiotensin Converting Enzyme Inhibitors
Angiotensin receptor blockers
Aldosterone antagonists
Renin inhibitors
a. Aliskiren (Tekturna, Rasilez)
Other potassium elevating agents
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| Name | Affiliation | Role |
|---|---|---|
| Michael M Segal, MD PhD | PhenoSolve, LLC | Principal Investigator |
| Mark Mintz, MD | CNNH & CRCNJ | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Research Center of New Jersey (CRCNJ) | Voorhees Township | New Jersey | 08043 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25447751 | Background | Infante MA, Moore EM, Nguyen TT, Fourligas N, Mattson SN, Riley EP. Objective assessment of ADHD core symptoms in children with heavy prenatal alcohol exposure. Physiol Behav. 2015 Sep 1;148:45-50. doi: 10.1016/j.physbeh.2014.10.014. Epub 2014 Oct 23. | |
| 18426576 | Background | Levitt JO. Practical aspects in the management of hypokalemic periodic paralysis. J Transl Med. 2008 Apr 21;6:18. doi: 10.1186/1479-5876-6-18. |
| Label | URL |
|---|---|
| Rozanski RJ, Primosch RE, Courts FJ (1988). Clinical efficacy of 1 and 2% solutions of lidocaine. Pediatr Dent.10:287-90 | View source |
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We plan to submit for publication descriptions of what was accomplished, and the evaluations as described in the study, including the incidence of lidocaine ineffectiveness in those with ADHD.
When the study is complete
open
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| ID | Term |
|---|---|
| D001289 | Attention Deficit Disorder with Hyperactivity |
| ID | Term |
|---|---|
| D019958 | Attention Deficit and Disruptive Behavior Disorders |
| D065886 | Neurodevelopmental Disorders |
| D001523 | Mental Disorders |
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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.
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The scoring of the lidocaine test is masked, using the coded identity of the tastes. The scoring will be done during the visit by the Scoring and Randomization Specialist so that the patient can be assigned to an intervention or control group to maintain equal numbers in treatment versus control groups. To prevent bias, the Scoring and Randomization Specialist will not be involved in any of the ADHD assessment steps and the patients will not be told about their lidocaine status until after all study testing is done. The subjects and other study personnel such as those doing the ADHD testing will be told not to discuss what they could or couldn't taste. Having scored the lidocaine test, the Scoring and Randomization Specialist will assign subjects to Intervention versus Control using a 1-to-1 allocation.
| Placebo oral capsule | Drug | Each subject will receive a dose of ~8 mg/kg of a placebo capsule |
|
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.
| 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 |
| 11143733 | Background | Nakai Y, Milgrom P, Mancl L, Coldwell SE, Domoto PK, Ramsay DS. Effectiveness of local anesthesia in pediatric dental practice. J Am Dent Assoc. 2000 Dec;131(12):1699-705. doi: 10.14219/jada.archive.2000.0115. |
| 24938135 | Background | Segal MM. We cannot say whether attention deficit hyperactivity disorder exists, but we can find its molecular mechanisms. Pediatr Neurol. 2014 Jul;51(1):15-6. doi: 10.1016/j.pediatrneurol.2014.04.014. Epub 2014 Apr 18. No abstract available. |
| 18174562 | Background | Segal MM, Rogers GF, Needleman HL, Chapman CA. Hypokalemic sensory overstimulation. J Child Neurol. 2007 Dec;22(12):1408-10. doi: 10.1177/0883073807307095. |
| 9212254 | Background | Segal MM, Douglas AF. Late sodium channel openings underlying epileptiform activity are preferentially diminished by the anticonvulsant phenytoin. J Neurophysiol. 1997 Jun;77(6):3021-34. doi: 10.1152/jn.1997.77.6.3021. |
| 23134619 | Background | Teicher MH, Polcari A, Fourligas N, Vitaliano G, Navalta CP. Hyperactivity persists in male and female adults with ADHD and remains a highly discriminative feature of the disorder: a case-control study. BMC Psychiatry. 2012 Nov 7;12:190. doi: 10.1186/1471-244X-12-190. |
| Saul R (2014) "ADHD Does Not Exist". HarperCollins. | View source |
| Segal MM, Jurkat-Rott K, Levitt J, Lehmann-Horn F (2014) Hypokalemic periodic paralysis - an owner's manual | View source |
| Segal MM (2015) Devices, Kits, and Methods for Determining Sensitivity to Anesthetics. US Patent Filing 62/210,747, Filed 09/14/2015 | View source |