Observational Study to Assess the Frequency of Lidocaine Ineffectiveness in Hard-to-treat ADHD

• Sponsor: PhenoSolve, LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04167189
• Collaborator: NeurAbilities (formerly CRCNJ) (Other)
• Enrollment: 28
• Location: 1
• Arm: 1
• Actual Duration (Months): 26.3
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

This work will assess the prevalence in hard-to-treat ADHD of the ineffectiveness of the anesthetic Lidocaine.

Condition or Disease	Intervention/Treatment	Phase
ADHD	Drug: Lidocaine gel	Early Phase 1

Detailed Description

Using a non-invasive, pain-free, taste-based approach to assess lidocaine effectiveness, the study will assess the frequency of ineffectiveness in the target population.

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Using a taste-based test before and after the application of lidocaine gel to the tongue, we will assess the degree to which lidocaine is effective at blocking taste in those with hard-to-treat ADHDUsing a taste-based test before and after the application of lidocaine gel to the tongue, we will assess the degree to which lidocaine is effective at blocking taste in those with hard-to-treat ADHD
• Masking: None (Open Label)
• Masking Description: The scoring of the lidocaine test is masked, using the coded identity of the tastes. The tastes will be assessed in random order. The subjects and other study personnel will be told not to discuss what the subject could or couldn't taste. Scoring will not be shared with the testing site until all testing is complete. This is one of the last studies with an IRB for each arm and site. Hence it appears to be a single arm, but the other arms are separately registered with ClinicalTrials.gov
• Primary Purpose: Health Services Research
• Official Title: Prevalence of Lidocaine Ineffectiveness in Those With Hard-to-treat ADHD
• Actual Study Start Date: Jan 20, 2018
• Actual Primary Completion Date: Mar 30, 2020
• Actual Study Completion Date: Mar 30, 2020

Arms and Interventions

Arm	Intervention/Treatment
Other: Observational study of prevalence in hard-to-treat ADHD Subjects will be tested with lidocaine gel.	Drug: Lidocaine gel; Septodont 5% oral lidocaine gel (NDC 0362-0221-10), 75 mg; Other Names: Intervention

Outcome Measures

Primary Outcome Measures

1. Observational Study: Number of Participants With Lidocaine Ineffectiveness by Taste Test in Hard-to-treat ADHD [on day of testing, approximately 30 minutes for clinic visit]

   Subjects will be asked to identify each taste and its intensity.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 7 Years to 49 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria: ADHD

Exclusion Criteria for both arms:

1. known adverse reactions to lidocaine

2. epilepsy, IQ <80, severe head trauma, birth weight <2270 grams, and severe autism;

3. treatment currently with potassium or potassium-elevating drugs such as renin-angiotensin-aldosterone blockers;

4. generalized anxiety disorders (but dental-specific anxiety will not be an exclusion because many of these individuals may be ones with anxiety because of painful dental experiences with lidocaine ineffectiveness);

5. mouth sores;

6. Ehlers Danlos syndrome, and

7. red hair.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	NeurAbilitis	Voorhees	New Jersey	United States	08043

Sponsors and Collaborators

• PhenoSolve, LLC
• NeurAbilities (formerly CRCNJ)

Investigators

• Principal Investigator: Michael Segal, MD PhD, PhenoSolve, LLC

Study Documents (Full-Text)

• Study Protocol - Aug 19, 2019

More Information

Additional Information:

• Saul R (2014) "ADHD Does Not Exist". HarperCollins
• Rozanski RJ, Primosch RE, Courts FJ (1988). Clinical efficacy of 1 and 2% solutions of lidocaine. Pediatr Dent.10:287-90
• Segal MM, Jurkat-Rott K, Levitt J, Lehmann-Horn F (2014) Hypokalemic periodic paralysis - an owner's manual
• Segal MM (2015) Devices, Kits, and Methods for Determining Sensitivity to Anesthetics. US Patent Filing 62/210,747, Filed 09/14/2015
• Companion study

Publications

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

• Responsible Party: PhenoSolve, LLC
• ClinicalTrials.gov Identifier: NCT04167189
• Other Study ID Numbers: 2019-01A
• First Posted: Nov 18, 2019
• Last Update Posted: Jul 2, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Lidocaine

Study Results

Participant Flow

Arm/Group Title	Hard-to-treat ADHD
Arm/Group Description	Subjects will be tested with Septodont 5% oral lidocaine gel (NDC 0362-0221-10), 75 mg pre-measured by compounding pharmacy and dispensed into blister pack
Period Title: Overall Study
STARTED	28
COMPLETED	28
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Hard-to-treat ADHD
Arm/Group Description	Subjects will be tested with Septodont 5% oral lidocaine gel (NDC 0362-0221-10), 75 mg pre-measured by compounding pharmacy and dispensed into blister pack
Overall Participants	28
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	16 (7.0)
Sex: Female, Male (Count of Participants)
Female	7 25%
Male	21 75%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 10.7%
Not Hispanic or Latino	25 89.3%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	22 78.6%
More than one race	6 21.4%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	28 100%
Hard-to-treat ADHD (does not respond to available ADHD drugs) (Count of Participants)
Count of Participants [Participants]	28 100%

Outcome Measures

1. Primary Outcome

Title	Observational Study: Number of Participants With Lidocaine Ineffectiveness by Taste Test in Hard-to-treat ADHD
Description	Subjects will be asked to identify each taste and its intensity.
Time Frame	on day of testing, approximately 30 minutes for clinic visit

Outcome Measure Data

Analysis Population Description

Study population vs. previously published studies in pediatric populations (Nakai et al, 2000)

Arm/Group Title	Hard-to-treat ADHD
Arm/Group Description	Subjects will be tested with Septodont 5% oral lidocaine gel (NDC 0362-0221-10), 75 mg pre-measured by compounding pharmacy and dispensed into blister pack
Measure Participants	28
Lidocaine effective (got numb)	1 3.6%
Lidocaine ineffective (did not get numb)	27 96.4%

Adverse Events

Time Frame	on day of testing, approximately 60 minutes for clinic visit
Arm/Group Title	Hard-to-treat ADHD
Arm/Group Description	Subjects will be tested with Septodont 5% oral lidocaine gel (NDC 0362-0221-10), 75 mg pre-measured by compounding pharmacy and dispensed into blister pack
All Cause Mortality
	Hard-to-treat ADHD
	Affected / at Risk (%)	# Events
Total	0/28 (0%)
Serious Adverse Events
	Hard-to-treat ADHD
	Affected / at Risk (%)	# Events
Total	0/28 (0%)
Other (Not Including Serious) Adverse Events
	Hard-to-treat ADHD
	Affected / at Risk (%)	# Events
Total	0/28 (0%)

Limitations/Caveats

This was an observational study without controls, as there were no controls available at the site. NeurAbilities is a clinic dedicated to treating patients with neurological diagnoses. To do statistics, the study will need to be repeated at a site that can provide controls.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.