Neurobiological Basis of Response to Vyvanse in Adults With ADHD: an fMRI Study of Brain Activation

• Sponsor: Jeffrey Newcorn (Other)
• Overall Status: Completed
• CT.gov ID: NCT01924429
• Collaborator: (none)
• Enrollment: 30
• Location: 1
• Arms: 2
• Duration (Months): 9
• Patients Per Site Per Month: 3.3

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the effects of Vyvanse, an FDA approved medication used in the treatment of Attention Deficit Hyperactivity Disorder (ADHD), on brain activity in adults with attention-deficit hyperactivity disorder (ADHD). Participants may qualify for participation in this study because they have ADHD and are willing to participate in two Functional Magnetic Resonance Imaging (fMRI) scans and receive Vyvanse for treatment of their symptoms. Another purpose of this study is to collect and bank samples of blood for research to examine how genes influence brain activation seen during the brain scans. The study also seeks to find out whether certain genes are related to ADHD. Participants' entire genetic makeup will not be determined from this sample.

Condition or Disease	Intervention/Treatment	Phase
ADHD	Drug: Lisdexamfetamine	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Basic Science
• Official Title: Neurobiological Basis of Response to Vyvanse in Adults With ADHD: an fMRI Study of Brain Activation
• Study Start Date: Mar 1, 2013
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: On Drug then off Drug Participants receive fMRI #1 on drug, #2 off drug Escalating stepped titration: 30, 50 or 70mg	Drug: Lisdexamfetamine; Escalating stepped dose titration: 30, 50 or 70mg; Other Names: Vyvanse
Experimental: Off drug then on drug Participants receive fMRI #1 off drug, #2 on drug Escalating stepped dose titration: 30, 50, 70mg	Drug: Lisdexamfetamine; Escalating stepped dose titration: 30, 50 or 70mg; Other Names: Vyvanse

Outcome Measures

Primary Outcome Measures

1. The Go/No-Go Task Percentage Assessed by fMRI [8 weeks]

   Performance Measures on the Go/No-Go Task assessed by fMRI as a Function of Trial Type, Face Emotion, and Drug Condition in Adults with Attention-Deficit/Hyperactivity Disorder. The Go/No-Go Task is a neuropsychological test that provides a direct measure of number of responses made that are "correct" or "incorrect". It is not a scale. Reported are the percentage of correct responses on that direct performance measure. 0% correct is worse than 100% correct.

2. fMRI Reaction Time [up to 6 weeks]

   Reaction-time, as measured by the reaction time test Go/No-Go Task as a Function of Trial Type, Face Emotion, and Drug Condition in Adults with Attention-Deficit/Hyperactivity Disorder

Secondary Outcome Measures

1. BRIEF-A [Baseline]

   Behavior Rating Inventory of Executive Function®-Adult Version (BRIEF-A): Norm Referenced Measure of Impaired Executive Functioning, reported in T-Scores (0 to 100, with 50 +/-1 SD = 'Normal', higher is worse, more impaired)

2. BRIEF-A [at one week]

   Behavior Rating Inventory of Executive Function®-Adult Version (BRIEF-A): Norm Referenced Measure of Impaired Executive Functioning, reported in T-Scores (higher is worse)

3. BRIEF-A [at 4 weeks]

   Behavior Rating Inventory of Executive Function®-Adult Version (BRIEF-A): Norm Referenced Measure of Impaired Executive Functioning, reported in T-Scores (higher is worse)

4. ASRS - Expanded [Baseline]

   ADHD and Related Symptoms Measure (ASRS): self report, reported as Sum of Responses (0-4 per item, higher = more impaired) 0-26 (normal range) and >27 (clinically significant symptoms).

5. ASRS - Expanded [at one week]

   ADHD and Related Symptoms Measure (ASRS): self report, reported as Sum of Responses (0-4 per item, higher = more impaired) 0-26 (normal range) and >27 (clinically significant symptoms).

6. ASRS - Expanded [at 4 weeks]

   ADHD and Related Symptoms Measure (ASRS): self report, reported as Sum of Responses (0-4 per item, higher = more impaired) 0-26 (normal range) and >27 (clinically significant symptoms).

7. WRAADS [Baseline]

   The Wender-Reimherr adult attention deficit disorder scale (WRAADS): Symptom measure for emotional functioning/lability, generally reported as Sum of Responses (0-2 per item, higher = more impaired). For this outcome measure, Average scores for particular questions were taken - specifically question 3, question 4, and question 5.

8. ADHD-RS-IV Combined Sum [Baseline]

   ADHD symptoms and severity. Norm referenced interview to assess severity and frequency of ADHD symptoms. 18 Items are scored 0-3 to reflect severity and frequency of ADHD symptoms, and a sum is taken. Full range from 0 to 54, with higher number indicating more symptoms and severity.

9. ADHD-Inattentive [4 weeks and 8 weeks]

   ADHD symptoms and severity - subscale for Inattentiveness. 9-item scale, each scored 0-3, with total from 0 to 27. Higher score indicates higher level of inattentiveness.

10. CGI-I [Baseline]

    Clinical Global Impressions - CGI-I: Clinical response was the Clinical Global Impression-Improvement scale (CGI-I). Lower CGI-I scores indicate greater improvement (1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse).

11. CGI-S [baseline]

    CGI-S: Severity of impairment due to ADHD was measured by the Clinical Global Impressions-Severity scale (CGI-S). Lower scores indicate less severe impairment from symptoms, with a CGI-I=1 indicating the person is "normal" with no impairment. (1= normal, not ill, 2= minimally ill, 3= mildly ill, 4= moderately ill, 5=markedly ill, 6=severely ill, 7= very severely ill)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Primary DSM-IV-TR diagnosis of adult ADHD (inattentive, hyperactive-impulsive or combined subtype), established via the ACDS v1.2.

• Must be between 18-55 years, inclusive.

• Provides written informed consent.

Exclusion Criteria:

• Lifetime or current diagnosis of bipolar disorder, schizophrenia or schizoaffective disorder.

• Current diagnosis of comorbid major depressive disorder, anxiety disorder or dysthymia or any controlled (i.e. requires pharmacological treatment) comorbid diagnosis. Participants with uncontrolled depressive or anxiety disorders may participate if, in the opinion of the Principal Investigator, the disorder will not confound the results of efficacy or safety assessments, increase risk to the participant or lead to difficulty complying with the protocol.

• Meets current DSM-IV-TR criteria for alcohol or any non-alcohol substance abuse or dependence disorder.

• Have organic brain disease (such as dementia) or traumatic brain injury residua. Have a history of seizure disorder (other than febrile seizures) or participants who have taken (or are currently taking) anticonvulsants for seizure control.

• Females who are currently pregnant or breast feeding, and women of child-bearing potential who are not currently using an adequate form of birth control.

• Participants with clinically significant abnormalities in ECG results that are deemed exclusionary in the opinion of the Principal Investigator will not be allowed in the trial.

• Participants who work the night shift or another schedule that would preclude beginning the daily dose of study medication in the morning.

• Participants with a positive urine drug result at Screening.

• Medical conditions limiting participation in the study.

• Documented history of intolerance or non-responsivity to methylphenidate or amphetamines.

• Have a medical condition that would, in the opinion of the study physician, make participation medically hazardous.

• ADHD, Not Otherwise Specified

• History of surgery involving metal implants, metal fragments in the eyes, braces, or a pacemaker.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029

Sponsors and Collaborators

• Jeffrey Newcorn

Investigators

• Principal Investigator: Jeffrey Newcorn, MD, Icahn School of Medicine at Mount Sinai

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jeffrey Newcorn, Associate Professor, Icahn School of Medicine at Mount Sinai
• ClinicalTrials.gov Identifier: NCT01924429
• Other Study ID Numbers: GCO 09-1186
• First Posted: Aug 16, 2013
• Last Update Posted: Jun 6, 2018
• Last Verified: May 1, 2018

• Keywords provided by Jeffrey Newcorn, Associate Professor, Icahn School of Medicine at Mount Sinai: Attention Deficit Hyperactivity Disorder; ADHD; fMRI; Imaging; Vyvanse; Stimulant Medication; Treatment; Clinical Trial; Adult
• Additional relevant MeSH terms: Lisdexamfetamine Dimesylate

Study Results

Participant Flow

Arm/Group Title	On Drug Then Off Drug	Off Drug Then on Drug
Arm/Group Description	Participants receive fMRI #1 on drug, #2 off drug Escalating stepped titration: 30, 50 or 70mg Lisdexamphetamine: Escalating stepped dose titration: 30, 50 or 70mg	Participants receive fMRI #1 off drug, #2 on drug Escalating stepped dose titration: 30, 50, 70mg Lisdexamphetamine: Escalating stepped dose titration: 30, 50 or 70mg
Period Title: Period 1 - First Intervention (4 Weeks)
STARTED	17	13
COMPLETED	17	13
NOT COMPLETED	0	0
Period Title: Period 1 - First Intervention (4 Weeks)
STARTED	17	13
COMPLETED	14	11
NOT COMPLETED	3	2
Period Title: Period 1 - First Intervention (4 Weeks)
STARTED	14	11
COMPLETED	14	11
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	On Drug, Then Off Drug	Off Drug, Then on Drug	Total
Arm/Group Description	fMRI #1 on drug, #2 off drug	fMRI #1 off drug, #2 on drug	Total of all reporting groups
Overall Participants	17	13	30
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35.46 (11.82)	37.27 (11.81)	35.84 (10.25)
Sex: Female, Male (Count of Participants)
Female	8 47.1%	5 38.5%	13 43.3%
Male	9 52.9%	8 61.5%	17 56.7%

Outcome Measures

1. Primary Outcome

Title	The Go/No-Go Task Percentage Assessed by fMRI
Description	Performance Measures on the Go/No-Go Task assessed by fMRI as a Function of Trial Type, Face Emotion, and Drug Condition in Adults with Attention-Deficit/Hyperactivity Disorder. The Go/No-Go Task is a neuropsychological test that provides a direct measure of number of responses made that are "correct" or "incorrect". It is not a scale. Reported are the percentage of correct responses on that direct performance measure. 0% correct is worse than 100% correct.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

Performance measures are done while participants are off drug and while on drug.

Arm/Group Title	Placebo	Lisdexamfetamine
Arm/Group Description	Participants received fMRI while off drug	Participants received fMRI while on drug
Measure Participants	25	25
Happy Correct Responses	91.7 (2.8)	97.0 (3.8)
Happy Correct Inhibitions	88.7 (9.4)	87.9 (11.5)
Sad Correct Responses	90.3 (7.7)	88.5 (10.6)
Sad Correct Inhibitions	84.4 (12.5)	86.7 (11.3)
Neutral Correct Responses	93.2 (12.2)	95.6 (5.8)
Neutral Correct Inhibitions	77.5 (12.3)	79.6 (11.6)

2. Primary Outcome

Title	fMRI Reaction Time
Description	Reaction-time, as measured by the reaction time test Go/No-Go Task as a Function of Trial Type, Face Emotion, and Drug Condition in Adults with Attention-Deficit/Hyperactivity Disorder
Time Frame	up to 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Lisdexamfetamine
Arm/Group Description	Participants received fMRI while off drug	Participants received fMRI while on drug
Measure Participants	25	25
Happy	532 (99)	519 (114)
Sad	533 (110)	509 (96)
Neutral	553 (109)	533 (104)

3. Secondary Outcome

Title	BRIEF-A
Description	Behavior Rating Inventory of Executive Function®-Adult Version (BRIEF-A): Norm Referenced Measure of Impaired Executive Functioning, reported in T-Scores (0 to 100, with 50 +/-1 SD = 'Normal', higher is worse, more impaired)
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	On Drug Then Off Drug	Off Drug Then on Drug
Arm/Group Description	Participants receive fMRI #1 on drug, #2 off drug Escalating stepped titration: 30, 50 or 70mg Lisdexamphetamine: Escalating stepped dose titration: 30, 50 or 70mg	Participants receive fMRI #1 off drug, #2 on drug Escalating stepped dose titration: 30, 50, 70mg Lisdexamphetamine: Escalating stepped dose titration: 30, 50 or 70mg
Measure Participants	14	11
Mean (Standard Deviation) [t-score]	66.64 (11.89)	73.5 (14.75)

4. Secondary Outcome

Title	BRIEF-A
Description	Behavior Rating Inventory of Executive Function®-Adult Version (BRIEF-A): Norm Referenced Measure of Impaired Executive Functioning, reported in T-Scores (higher is worse)
Time Frame	at one week

Outcome Measure Data

Analysis Population Description

not collected

Arm/Group Title	On Drug Then Off Drug	Off Drug Then on Drug
Arm/Group Description	Participants receive fMRI #1 on drug, #2 off drug Escalating stepped titration: 30, 50 or 70mg Lisdexamphetamine: Escalating stepped dose titration: 30, 50 or 70mg	Participants receive fMRI #1 off drug, #2 on drug Escalating stepped dose titration: 30, 50, 70mg Lisdexamphetamine: Escalating stepped dose titration: 30, 50 or 70mg
Measure Participants	0	0

5. Secondary Outcome

Title	BRIEF-A
Description	Behavior Rating Inventory of Executive Function®-Adult Version (BRIEF-A): Norm Referenced Measure of Impaired Executive Functioning, reported in T-Scores (higher is worse)
Time Frame	at 4 weeks

Outcome Measure Data

Analysis Population Description

not collected

Arm/Group Title	On Drug Then Off Drug	Off Drug Then on Drug
Arm/Group Description	Participants receive fMRI #1 on drug, #2 off drug Escalating stepped titration: 30, 50 or 70mg Lisdexamphetamine: Escalating stepped dose titration: 30, 50 or 70mg	Participants receive fMRI #1 off drug, #2 on drug Escalating stepped dose titration: 30, 50, 70mg Lisdexamphetamine: Escalating stepped dose titration: 30, 50 or 70mg
Measure Participants	0	0

6. Secondary Outcome

Title	ASRS - Expanded
Description	ADHD and Related Symptoms Measure (ASRS): self report, reported as Sum of Responses (0-4 per item, higher = more impaired) 0-26 (normal range) and >27 (clinically significant symptoms).
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	On Drug Then Off Drug	Off Drug Then on Drug
Arm/Group Description	Participants receive fMRI #1 on drug, #2 off drug Escalating stepped titration: 30, 50 or 70mg Lisdexamphetamine: Escalating stepped dose titration: 30, 50 or 70mg	Participants receive fMRI #1 off drug, #2 on drug Escalating stepped dose titration: 30, 50, 70mg Lisdexamphetamine: Escalating stepped dose titration: 30, 50 or 70mg
Measure Participants	14	11
Mean (Standard Deviation) [units on a scale]	83.7 (25.59)	86 (4.24)

7. Secondary Outcome

Title	ASRS - Expanded
Description	ADHD and Related Symptoms Measure (ASRS): self report, reported as Sum of Responses (0-4 per item, higher = more impaired) 0-26 (normal range) and >27 (clinically significant symptoms).
Time Frame	at one week

Outcome Measure Data

Analysis Population Description

not collected

Arm/Group Title	On Drug Then Off Drug	Off Drug Then on Drug
Arm/Group Description	Participants receive fMRI #1 on drug, #2 off drug Escalating stepped titration: 30, 50 or 70mg Lisdexamphetamine: Escalating stepped dose titration: 30, 50 or 70mg	Participants receive fMRI #1 off drug, #2 on drug Escalating stepped dose titration: 30, 50, 70mg Lisdexamphetamine: Escalating stepped dose titration: 30, 50 or 70mg
Measure Participants	0	0

8. Secondary Outcome

Title	ASRS - Expanded
Description	ADHD and Related Symptoms Measure (ASRS): self report, reported as Sum of Responses (0-4 per item, higher = more impaired) 0-26 (normal range) and >27 (clinically significant symptoms).
Time Frame	at 4 weeks

Outcome Measure Data

Analysis Population Description

not collected

Arm/Group Title	On Drug Then Off Drug	Off Drug Then on Drug
Arm/Group Description	Participants receive fMRI #1 on drug, #2 off drug Escalating stepped titration: 30, 50 or 70mg Lisdexamphetamine: Escalating stepped dose titration: 30, 50 or 70mg	Participants receive fMRI #1 off drug, #2 on drug Escalating stepped dose titration: 30, 50, 70mg Lisdexamphetamine: Escalating stepped dose titration: 30, 50 or 70mg
Measure Participants	0	0

9. Secondary Outcome

Title	WRAADS
Description	The Wender-Reimherr adult attention deficit disorder scale (WRAADS): Symptom measure for emotional functioning/lability, generally reported as Sum of Responses (0-2 per item, higher = more impaired). For this outcome measure, Average scores for particular questions were taken - specifically question 3, question 4, and question 5.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	On Drug Then Off Drug	Off Drug Then on Drug
Arm/Group Description	Participants receive fMRI #1 on drug, #2 off drug Escalating stepped titration: 30, 50 or 70mg Lisdexamphetamine: Escalating stepped dose titration: 30, 50 or 70mg	Participants receive fMRI #1 off drug, #2 on drug Escalating stepped dose titration: 30, 50, 70mg Lisdexamphetamine: Escalating stepped dose titration: 30, 50 or 70mg
Measure Participants	14	11
Question 3	0.80 (0.86)	0.94 (0.745)
Question 4	1.27 (1.22)	1.47 (1.23)
Question 5	1.13 (1.35)	1.82 (1.19)

10. Secondary Outcome

Title	ADHD-RS-IV Combined Sum
Description	ADHD symptoms and severity. Norm referenced interview to assess severity and frequency of ADHD symptoms. 18 Items are scored 0-3 to reflect severity and frequency of ADHD symptoms, and a sum is taken. Full range from 0 to 54, with higher number indicating more symptoms and severity.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	On Drug Then Off Drug	Off Drug Then on Drug
Arm/Group Description	Participants receive fMRI #1 on drug, #2 off drug Escalating stepped titration: 30, 50 or 70mg Lisdexamphetamine: Escalating stepped dose titration: 30, 50 or 70mg	Participants receive fMRI #1 off drug, #2 on drug Escalating stepped dose titration: 30, 50, 70mg Lisdexamphetamine: Escalating stepped dose titration: 30, 50 or 70mg
Measure Participants	14	11
On Drug	11.00 (6.98)	13.67 (11.64)
Placebo	25.65 (8.53)	31.00 (14.80)

11. Secondary Outcome

Title	ADHD-Inattentive
Description	ADHD symptoms and severity - subscale for Inattentiveness. 9-item scale, each scored 0-3, with total from 0 to 27. Higher score indicates higher level of inattentiveness.
Time Frame	4 weeks and 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	On Drug Then Off Drug	Off Drug Then on Drug
Arm/Group Description	Participants receive fMRI #1 on drug, #2 off drug Escalating stepped titration: 30, 50 or 70mg Lisdexamphetamine: Escalating stepped dose titration: 30, 50 or 70mg	Participants receive fMRI #1 off drug, #2 on drug Escalating stepped dose titration: 30, 50, 70mg Lisdexamphetamine: Escalating stepped dose titration: 30, 50 or 70mg
Measure Participants	14	11
On drug	7.36 (4.53)	8.83 (7.63)
Placebo	18.94 (6.21)	19.2 (5.07)

12. Secondary Outcome

Title	CGI-I
Description	Clinical Global Impressions - CGI-I: Clinical response was the Clinical Global Impression-Improvement scale (CGI-I). Lower CGI-I scores indicate greater improvement (1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse).
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	On Drug Then Off Drug	Off Drug Then on Drug
Arm/Group Description	Participants receive fMRI #1 on drug, #2 off drug Escalating stepped titration: 30, 50 or 70mg Lisdexamphetamine: Escalating stepped dose titration: 30, 50 or 70mg	Participants receive fMRI #1 off drug, #2 on drug Escalating stepped dose titration: 30, 50, 70mg Lisdexamphetamine: Escalating stepped dose titration: 30, 50 or 70mg
Measure Participants	14	11
Mean (Standard Deviation) [units on a scale]	1.88 (1.13)	2.00 (1.41)

13. Secondary Outcome

Title	CGI-S
Description	CGI-S: Severity of impairment due to ADHD was measured by the Clinical Global Impressions-Severity scale (CGI-S). Lower scores indicate less severe impairment from symptoms, with a CGI-I=1 indicating the person is "normal" with no impairment. (1= normal, not ill, 2= minimally ill, 3= mildly ill, 4= moderately ill, 5=markedly ill, 6=severely ill, 7= very severely ill)
Time Frame	baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	On Drug Then Off Drug	Off Drug Then on Drug
Arm/Group Description	Participants receive fMRI #1 on drug, #2 off drug Escalating stepped titration: 30, 50 or 70mg Lisdexamphetamine: Escalating stepped dose titration: 30, 50 or 70mg	Participants receive fMRI #1 off drug, #2 on drug Escalating stepped dose titration: 30, 50, 70mg Lisdexamphetamine: Escalating stepped dose titration: 30, 50 or 70mg
Measure Participants	14	11
Mean (Standard Deviation) [units on a scale]	4.9 (1.0)	4.95 (0.9)

Adverse Events

Arm/Group Title	On Drug, Then Off Drug		Off Drug, Then on Drug
Arm/Group Description	Participants receive fMRI #1 on drug, #2 off drug Escalating stepped titration: 30, 50 or 70mg Lisdexamphetamine: Escalating stepped dose titration: 30, 50 or 70mg		Participants receive fMRI #1 off drug, #2 on drug Escalating stepped dose titration: 30, 50, 70mg Lisdexamphetamine: Escalating stepped dose titration: 30, 50 or 70mg
All Cause Mortality
	On Drug, Then Off Drug		Off Drug, Then on Drug
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/11 (0%)
Serious Adverse Events
	On Drug, Then Off Drug		Off Drug, Then on Drug
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/11 (0%)
Other (Not Including Serious) Adverse Events
	On Drug, Then Off Drug		Off Drug, Then on Drug
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/14 (100%)		11/11 (100%)
General disorders
Incidental finding on brain scan	0/14 (0%)		1/11 (9.1%)
Incidental Physical finding	3/14 (21.4%)		0/11 (0%)
Insomnia	2/14 (14.3%)		1/11 (9.1%)
Heart Racing	1/14 (7.1%)		0/11 (0%)
Dry mouth	1/14 (7.1%)		2/11 (18.2%)
feeling agitated	1/14 (7.1%)		0/11 (0%)
Tired	1/14 (7.1%)		0/11 (0%)
Anxious	1/14 (7.1%)		2/11 (18.2%)
Headache	1/14 (7.1%)		2/11 (18.2%)
Restless	1/14 (7.1%)		0/11 (0%)
Seasonal allergies	0/14 (0%)		2/11 (18.2%)
Subjectively feeling "stuck"	0/14 (0%)		1/11 (9.1%)
Suspiciousness	1/14 (7.1%)		0/11 (0%)
Reduced Appetite	1/14 (7.1%)		0/11 (0%)
Bruxism	0/14 (0%)		1/11 (9.1%)
Musculoskeletal and connective tissue disorders
Backache	1/14 (7.1%)		0/11 (0%)
Skin and subcutaneous tissue disorders
Skin Sores	1/14 (7.1%)		0/11 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.