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

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ClinicalTrials.gov Identifier: NCT03563573
Recruitment Status : Unknown
Verified June 2018 by AlkaliDx, Inc..
Recruitment status was:  Enrolling by invitation
First Posted : June 20, 2018
Last Update Posted : June 20, 2018
Sponsor:
Information provided by (Responsible Party):
AlkaliDx, Inc.

Tracking Information
First Submitted Date  ICMJE May 15, 2018
First Posted Date  ICMJE June 20, 2018
Last Update Posted Date June 20, 2018
Estimated Study Start Date  ICMJE July 1, 2018
Estimated Primary Completion Date November 4, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 14, 2018)
Prevalence of lidocaine ineffectiveness in those with ADHD [ Time Frame: Baseline ]
Investigator assesses identification and intensity of tastes (such as sweet) before and after application of oral lidocaine gel to the tongue.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: June 14, 2018)
  • Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 1-2 hours after intervention ]
    Investigator documentation of adverse reactions to either lidocaine or potassium
  • Other discomforts [ Time Frame: 1-2 hours after intervention ]
    Investigator documentation of complaints or minor discomforts
  • Change in ADHD-RS questionnaires [ Time Frame: Baseline 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 Questionnaire [ Time Frame: Baseline 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 System [ Time Frame: Baseline 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)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Single-dose Potassium Supplementation in Patients With ADHD for Whom the Anesthetic Lidocaine is Ineffective
Official Title  ICMJE Single-dose Potassium Supplementation in ADHD Patients With Lidocaine Ineffectiveness
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

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
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.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
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.
Primary Purpose: Treatment
Condition  ICMJE ADHD
Intervention  ICMJE
  • 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.
  • Drug: Placebo oral capsule
    Each subject will receive a dose of ~8 mg/kg of a placebo capsule
Study Arms  ICMJE
  • Active Comparator: Lidocaine-effective ADHD: Intervention
    Single-dose potassium gluconate oral capsule intervention for ADHD subjects for whom lidocaine is effective
    Intervention: Drug: Potassium Gluconate Oral Capsule
  • Placebo Comparator: Lidocaine-effective ADHD: Placebo
    Single-dose placebo oral capsule intervention for ADHD subjects for whom lidocaine is effective
    Intervention: Drug: Placebo oral capsule
  • Active Comparator: Lidocaine-ineffective ADHD: Intervention
    Single-dose potassium gluconate oral capsule intervention for ADHD subjects for whom lidocaine is ineffective
    Intervention: Drug: Potassium Gluconate Oral Capsule
  • Placebo Comparator: Lidocaine-ineffective ADHD: placebo
    Single-dose placebo oral capsule intervention for ADHD subjects for whom lidocaine is ineffective
    Intervention: Drug: Placebo oral capsule
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: June 14, 2018)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2018
Estimated Primary Completion Date November 4, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 13 Years to 49 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03563573
Other Study ID Numbers  ICMJE 2017-01A
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: We plan to submit for publication descriptions of what was accomplished, and the evaluations as described in the study, including the incidence of lidocaine ineffectiveness in those with ADHD.
Supporting Materials: Clinical Study Report (CSR)
Time Frame: When the study is complete
Access Criteria: open
Responsible Party AlkaliDx, Inc.
Study Sponsor  ICMJE AlkaliDx, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Michael M Segal, MD PhD PhenoSolve, LLC
Principal Investigator: Mark Mintz, MD CNNH & CRCNJ
PRS Account AlkaliDx, Inc.
Verification Date June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP