Clinical trial NCT03563573: Single-dose Potassium Supplementation in Patients With ADHD for Whom the Anesthetic Lidocaine is Ineffective
Official title: Single-dose Potassium Supplementation in ADHD Patients With Lidocaine Ineffectiveness
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: ADHD
Keywords: Conditions in which lidocaine is ineffective
Lead sponsor: AlkaliDx, Inc.
Sponsor class: INDUSTRY
First posted: 2018-06-20
Enrollment: 100
Sex: ALL
Minimum age (years): 13
Maximum age (years): 49
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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 purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Prevalence of lidocaine ineffectiveness in those with ADHD
timeFrame: Baseline
Secondary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: 1-2 hours after intervention
measure: Other discomforts
timeFrame: 1-2 hours after intervention
measure: Change in ADHD-RS questionnaires
timeFrame: Baseline and ~1-2 hours later, 1 hour after intervention
measure: Change in Clinical Global Impression Physician Completed Questionnaire
timeFrame: Baseline and ~1-2 hours later, 1 hour after intervention
measure: Change in scores using Quotient ADHD System
timeFrame: Baseline and ~1 hour after intervention
Other outcomes:
Locations:
city: Voorhees
country: United States
facility: Clinical Research Center of New Jersey (CRCNJ)
state: New Jersey
Study officials:
affiliation: PhenoSolve, LLC
name: Michael M Segal, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: CNNH & CRCNJ
name: Mark Mintz, MD
role: PRINCIPAL_INVESTIGATOR
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