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

NCT ID: NCT03563573

Last Updated: 2018-06-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

PHASE1/PHASE2

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-07-01

Study Completion Date

2018-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

ADHD

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
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.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Lidocaine-effective ADHD: Intervention

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

Group Type ACTIVE_COMPARATOR

Potassium Gluconate Oral Capsule

Intervention Type 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: Placebo

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

Group Type PLACEBO_COMPARATOR

Placebo oral capsule

Intervention Type DRUG

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

Lidocaine-ineffective ADHD: Intervention

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

Group Type ACTIVE_COMPARATOR

Potassium Gluconate Oral Capsule

Intervention Type 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-ineffective ADHD: placebo

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

Group Type PLACEBO_COMPARATOR

Placebo oral capsule

Intervention Type DRUG

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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type DRUG

Placebo oral capsule

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

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

13 Years

Maximum Eligible Age

49 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

AlkaliDx, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Michael M Segal, MD PhD

Role: PRINCIPAL_INVESTIGATOR

PhenoSolve, LLC

Mark Mintz, MD

Role: PRINCIPAL_INVESTIGATOR

CNNH & CRCNJ

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Clinical Research Center of New Jersey (CRCNJ)

Voorhees Township, New Jersey, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 25447751 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18426576 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11143733 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24938135 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 18174562 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9212254 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23134619 (View on PubMed)

Related Links

Access external resources that provide additional context or updates about the study.

https://pdfs.semanticscholar.org/1778/f693dc7dd257ab98a96b5bf03408d9cef3eb.pdf

Rozanski RJ, Primosch RE, Courts FJ (1988). Clinical efficacy of 1 and 2% solutions of lidocaine. Pediatr Dent.10:287-90

https://www.amazon.com/ADHD-Does-Not-Exist-Hyperactivity/dp/006226673X

Saul R (2014) "ADHD Does Not Exist". HarperCollins.

http://simulconsult.com/resources/hypopp.html

Segal MM, Jurkat-Rott K, Levitt J, Lehmann-Horn F (2014) Hypokalemic periodic paralysis - an owner's manual

https://patents.google.com/patent/WO2017035470A1/en

Segal MM (2015) Devices, Kits, and Methods for Determining Sensitivity to Anesthetics. US Patent Filing 62/210,747, Filed 09/14/2015

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2017-01A

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.