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

NCT03563573 | Unknown Phase 1 FDA Drug

• 1 other identifier: 2017-01A
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

ADHD

Keywords

Conditions in which lidocaine is ineffective

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  1-2 hours after intervention

• Other discomforts

  1-2 hours after intervention

• Change in ADHD-RS questionnaires

  Baseline and ~1-2 hours later, 1 hour after intervention

• Change in Clinical Global Impression Physician Completed Questionnaire

  Baseline and ~1-2 hours later, 1 hour after intervention

• Change in scores using Quotient ADHD System

  Baseline and ~1 hour after intervention

Study Arms (4)

Lidocaine-effective ADHD: Intervention

ACTIVE COMPARATOR

Single-dose potassium gluconate oral capsule intervention for ADHD subjects for whom lidocaine is effective

Drug: Potassium Gluconate Oral Capsule

Lidocaine-effective ADHD: Placebo

PLACEBO COMPARATOR

Single-dose placebo oral capsule intervention for ADHD subjects for whom lidocaine is effective

Drug: Placebo oral capsule

Lidocaine-ineffective ADHD: Intervention

ACTIVE COMPARATOR

Single-dose potassium gluconate oral capsule intervention for ADHD subjects for whom lidocaine is ineffective

Drug: Potassium Gluconate Oral Capsule

Lidocaine-ineffective ADHD: placebo

PLACEBO COMPARATOR

Single-dose placebo oral capsule intervention for ADHD subjects for whom lidocaine is ineffective

Drug: Placebo oral capsule

Interventions

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.

Lidocaine-effective ADHD: Intervention; Lidocaine-ineffective ADHD: Intervention

Placebo oral capsule DRUG

Each subject will receive a dose of \~8 mg/kg of a placebo capsule

Lidocaine-effective ADHD: Placebo; Lidocaine-ineffective ADHD: placebo

Eligibility Criteria

• Age: 13 Years - 49 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• AlkaliDx, Inc.: lead

Study Sites (1)

Clinical Research Center of New Jersey (CRCNJ)

Voorhees Township, New Jersey, 08043, United States

Location

Related Publications (7)

• 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.

  PMID: 25447751 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.

  PMID: 18426576 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.

  PMID: 11143733 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.

  PMID: 24938135 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.

  PMID: 18174562 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.

  PMID: 9212254 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.

  PMID: 23134619 BACKGROUND

Related Links

• Rozanski RJ, Primosch RE, Courts FJ (1988). Clinical efficacy of 1 and 2% solutions of lidocaine. Pediatr Dent.10:287-90
• Saul R (2014) "ADHD Does Not Exist". HarperCollins.
• Segal MM, Jurkat-Rott K, Levitt J, Lehmann-Horn F (2014) Hypokalemic periodic paralysis - an owner's manual
• Segal MM (2015) Devices, Kits, and Methods for Determining Sensitivity to Anesthetics. US Patent Filing 62/210,747, Filed 09/14/2015

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Study Officials

• Michael M Segal, MD PhD

  PhenoSolve, LLC

  PRINCIPAL INVESTIGATOR

• Mark Mintz, MD

  CNNH & CRCNJ

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 15, 2018
• First Posted: June 20, 2018
• Study Start: July 1, 2018
• Primary Completion: November 4, 2018
• Study Completion: December 31, 2018
• Last Updated: June 20, 2018

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: When the study is complete
• Access Criteria: open

Locations

US (1)