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

Phase 1
Conditions
ADHD
Interventions
Drug: Placebo oral capsule
Registration Number
NCT03563573
Lead Sponsor
AlkaliDx, Inc.
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.

Detailed Description

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

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
100
Inclusion Criteria
  1. Previously documented ADHD diagnosis
  2. 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
  1. Well treated with existing ADHD medication
  2. Epilepsy
  3. IQ less than 80
  4. Severe head trauma that led to loss of consciousness for more than an hour or required surgery
  5. Birth weight below 5 pounds or 2270 grams
  6. Severe autism (milder conditions described as Asperger syndrome or "high-functioning autism" are not excluded)
  7. 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
  8. Mouth lesions, known to temporarily interfere with lidocaine effectiveness
  9. Renal disease or abnormal kidney function or receiving dialysis
  10. 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.
  11. Heart arrhythmia, known or evident on ECG
  12. Known intolerance or allergy to lidocaine
  13. Already taking supplemental potassium or renin angiotensin aldosterone inhibitors or other potassium elevating agents (see list below)

Angiotensin Converting Enzyme Inhibitors

  1. Alacepril (not available in US)
  2. Benazepril (Lotensin)
  3. Captopril (trade name Capoten)
  4. Cilazapril (Inhibace)
  5. Delapril (not available in US)
  6. Enalapril (Vasotec/Renitec)
  7. Fosinopril (Fositen/Monopril)
  8. Imidapril (Tanatril)
  9. Lisinopril (Listril/Lopril/Novatec/Prinivil/Zestril)
  10. Moexipril (Univasc)
  11. Perindopril (Coversyl/Aceon/Perindo)
  12. Quinapril (Accupril)
  13. Ramipril (Altace/Prilace/Ramace/Ramiwin/Triatec/Tritace)
  14. Spirapril (Renormax)
  15. Temocapril (not available in US)
  16. Teprotide (but not active by oral administration and not used in US)
  17. Trandolapril (Mavik/Odrik/Gopten)
  18. Zofenopril

Angiotensin receptor blockers

  1. Azilsartan (Edarbi)
  2. Candesartan (Atacand)
  3. Eprosartan (Teveten)
  4. Fimasartan (Kanarb)
  5. Irbesartan (Avapro)
  6. Losartan (Cozaar)
  7. Olmesartan (Benicar/Olmetec)
  8. Telmisartan (Micardis)
  9. Valsartan (Diovan)

Aldosterone antagonists

  1. Spironolactone (Aldactone)
  2. Eplerenone (Inspra)

Renin inhibitors

a. Aliskiren (Tekturna, Rasilez)

Other potassium elevating agents

  1. Antibiotics, including penicillin G and trimethoprim
  2. Azole antifungals
  3. Beta-blockers
  4. Herbal supplements, including milkweed, lily of the valley, Siberian ginseng, Hawthorn berries
  5. Heparin
  6. Nonsteroidal anti-inflammatory medications (NSAIDs)
  7. Oral contraceptives containing drospirenone

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Lidocaine-effective ADHD: InterventionPotassium Gluconate Oral CapsuleSingle-dose potassium gluconate oral capsule intervention for ADHD subjects for whom lidocaine is effective
Lidocaine-effective ADHD: PlaceboPlacebo oral capsuleSingle-dose placebo oral capsule intervention for ADHD subjects for whom lidocaine is effective
Lidocaine-ineffective ADHD: InterventionPotassium Gluconate Oral CapsuleSingle-dose potassium gluconate oral capsule intervention for ADHD subjects for whom lidocaine is ineffective
Lidocaine-ineffective ADHD: placeboPlacebo oral capsuleSingle-dose placebo oral capsule intervention for ADHD subjects for whom lidocaine is ineffective
Primary Outcome Measures
NameTimeMethod
Prevalence of lidocaine ineffectiveness in those with ADHDBaseline

Investigator assesses identification and intensity of tastes (such as sweet) before and after application of oral lidocaine gel to the tongue.

Secondary Outcome Measures
NameTimeMethod
Number of participants with treatment-related adverse events as assessed by CTCAE v4.01-2 hours after intervention

Investigator documentation of adverse reactions to either lidocaine or potassium

Other discomforts1-2 hours after intervention

Investigator documentation of complaints or minor discomforts

Change in ADHD-RS questionnairesBaseline and ~1-2 hours later, 1 hour after intervention

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.

1. Carelessness

2. Difficulty sustaining attention in activities

3. No follow through

4. Can't organize

5. Avoids/dislikes tasks requiring sustained mental effort

6. Loses Important items

7. Easily distractible

8. Forgetful in daily activities

Change in Clinical Global Impression Physician Completed QuestionnaireBaseline and ~1-2 hours later, 1 hour after intervention

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

Change in scores using Quotient ADHD SystemBaseline and ~1 hour after intervention

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)

Trial Locations

Locations (1)

Clinical Research Center of New Jersey (CRCNJ)

🇺🇸

Voorhees, New Jersey, United States

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