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

ADHD Clinical Trial

Official title:

Single-dose Potassium Supplementation in ADHD Patients With Lidocaine Ineffectiveness

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT03563573
• Other study ID #: 2017-01A
• Status: Enrolling by invitation
• Phase: Phase 1/Phase 2
• Start date: July 1, 2018
• Est. completion date: December 31, 2018

Study information

• Verified date: June 2018
• Source: AlkaliDx, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Enrolling by invitation
• Enrollment: 100
• Est. completion date: December 31, 2018
• Est. primary completion date: November 4, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years to 49 Years

Eligibility

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

Related Conditions & MeSH terms

• ADHD

Intervention

Drug:
• Potassium Gluconate Oral Capsule
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.
• Placebo oral capsule
Each subject will receive a dose of ~8 mg/kg of a placebo capsule

Locations

Country	Name	City	State
United States	Clinical Research Center of New Jersey (CRCNJ)	Voorhees	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
AlkaliDx, Inc.

Country where clinical trial is conducted

United States, 

References & 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. — View Citation

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. Erratum in: J Transl Med. 2014;12:198. Dosage error in article text. — View Citation

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. — View Citation

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. — View Citation

Segal MM, Rogers GF, Needleman HL, Chapman CA. Hypokalemic sensory overstimulation. J Child Neurol. 2007 Dec;22(12):1408-10. doi: 10.1177/0883073807307095. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Other discomforts	Investigator documentation of complaints or minor discomforts	1-2 hours after intervention
Secondary	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
Secondary	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
Secondary	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

External 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 (2015) Devices, Kits, and Methods for Determining Sensitivity to Anesthetics. US Patent Filing 62/210,747, Filed 09/14/2015
•   Segal MM, Jurkat-Rott K, Levitt J, Lehmann-Horn F (2014) Hypokalemic periodic paralysis - an owner's manual