Modafinil for Attention Deficits

(LC Trial)

Recruiting in Sacramento (>99 mi)

Overseen By Jared Borden, MA

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: University of California, Davis

Must not be taking: Psychotropic medications

Disqualifiers: Schizophrenia, Neurological disorder, Drug use, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1-2 weeks

40 Participants Needed

Trial Summary

What is the purpose of this trial?

The norepinephrine-producing locus coeruleus (LC) is thought to be central to a wide array of cognitive functions, like attention and goal pursuit, and has been implicated in dysfunctions including attention deficit hyperactivity disorder and schizophrenia. The goal of this proposal is to develop methods that permit measurement of activity in the human LC. Because the LC is small and located in the pons, the Investigators will use high resolution magnetic resonance imaging techniques tailored to the brainstem environment, including neuromelanin-sensitive images shown to delineate the LC, combined with pharmacological manipulation to confirm the location of functional activity.

Will I have to stop taking my current medications?

The trial requires that you stop taking any psychotropic medications (drugs that affect your mind) at least a week before participating.

What data supports the effectiveness of the drug modafinil for attention deficits?

Research shows that modafinil can improve symptoms of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents, with studies indicating significant improvements in attention and behavior compared to a placebo. Additionally, a meta-analysis found that modafinil significantly improved ADHD symptoms at home and school. ^{1 2 3 4 5}

Is modafinil generally safe for humans?

Modafinil is generally considered safe for use in adults, but there are reports of serious skin reactions, which are rare but important to be aware of. It has been tested in various settings, but more studies are needed to fully understand its long-term safety, especially in children. ^{1 6 7 8 9}

How does the drug modafinil differ from other treatments for attention deficits?

Modafinil is unique because it is a wake-promoting drug that enhances cognitive functions like working memory and attention, with a low risk of addiction. Unlike traditional stimulants, it affects multiple brain systems, including catecholamines and serotonin, making it a promising option for cognitive dysfunction in various neuropsychiatric disorders. ^{1 3 10 11 12}

Eligibility Criteria

This trial is for healthy adults aged 18-60 who can undergo MRI scans. It's not suitable for those with metal implants, pacemakers, or claustrophobia. Pregnant or nursing individuals, people on psychotropic meds within the last week, and those with a history of severe mental health issues or substance abuse are excluded.

Inclusion Criteria

I am between 18 and 60 years old.

I am a healthy adult without any developmental delays.

Exclusion Criteria

You have a history of schizophrenia or other forms of mental illness that affect your thoughts and perception.

You have a significant neurological disorder or have had a serious problem with alcohol or drug abuse within the last 5 years.

You are allergic or sensitive to any ingredients in modafinil or its form.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive modafinil or placebo in a double-blind, placebo-controlled crossover study to measure LC activity using fMRI and pupillometry

1-2 weeks

Multiple visits for drug administration and imaging

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Modafinil

Trial Overview The study tests Modafinil's effect on attention by using advanced brain imaging to observe activity in the locus coeruleus (LC), which is involved in cognitive functions and may be linked to disorders like ADHD and schizophrenia.

Participant Groups

Group I: Modafinil Active Control 1 Intervention

Single oral dose (200 mg) of medication versus placebo given to healthy control subjects

Group II: Placebo Placebo Group 1 Intervention

Oral placebo

Who Is Running the Clinical Trial?

University of California, Davis

Lead Sponsor

Trials

958

Recruited

4,816,000+

Findings from Research

Modafinil has been shown to significantly improve symptoms of ADHD and cognitive function in patients, based on a review of 4 randomized clinical trials.

The medication has a favorable safety profile, with common side effects like insomnia and headache occurring in about 20% of patients, but its long-term efficacy remains uncertain and requires further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of modafinil for the treatment of attention deficit/hyperactivity disorder. Lindsay, SE., Gudelsky, GA., Heaton, PC.[2018]

Modafinil significantly improved ADHD symptoms in children and adolescents, as shown by a meta-analysis of five randomized, double-blind, placebo-controlled trials, with effect sizes of -0.77 for home ratings and -0.71 for school ratings on the ADHD Rating Scale-IV.

While modafinil was effective, it was associated with higher rates of decreased appetite and insomnia compared to placebo, but it did not cause significant increases in heart rate or blood pressure, indicating a relatively safe profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modafinil for the treatment of attention-deficit/hyperactivity disorder: A meta-analysis. Wang, SM., Han, C., Lee, SJ., et al.[2018]

In a study of 78 outpatients, modafinil was found to significantly improve depression symptoms when used alongside antidepressants, as indicated by improvements in various rating scales (p < 0.01 to p < 0.001).

Modafinil was well tolerated and effectively enhanced wakefulness and daily functioning, suggesting it could be a beneficial adjunctive treatment for patients experiencing fatigue or sleepiness while on antidepressant therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modafinil as adjunctive therapy in depressed outpatients. Nasr, S.[2019]

In an 8-week open-label study involving 220 children and adolescents with ADHD, modafinil significantly improved ADHD symptoms across various rating scales, demonstrating its continued efficacy after an initial 4-week double-blind trial.

Modafinil was well tolerated, with common side effects being insomnia (13%) and headache (10%), and no significant adverse effects on vital signs or physical health were observed, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modafinil in children and adolescents with attention-deficit/hyperactivity disorder: a preliminary 8-week, open-label study. Boellner, SW., Earl, CQ., Arora, S.[2018]

In a study of 11 children with ADHD, once-daily dosing of modafinil for an average of 4.6 weeks led to significant improvements in attention and behavior, as measured by various ADHD rating scales.

While one child experienced an adverse event that resolved after stopping the medication, other side effects were mild and manageable, suggesting that modafinil could be a safe and effective treatment option for ADHD in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of modafinil in children with attention-deficit/hyperactivity disorder: an open-label study. Rugino, TA., Copley, TC.[2018]

In a double-blind randomized cross-over trial involving 45 adults with ADHD, methylphenidate demonstrated a response rate of 38-51%, significantly higher than the 7-18% response rate observed with placebo (p<0.05).

Methylphenidate was found to be effective and well-tolerated, with only a few mild side effects reported, suggesting it is a safe short-term treatment option for adult ADHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of methylphenidate in 45 adults with attention-deficit/hyperactivity disorder. A randomized placebo-controlled double-blind cross-over trial. Kooij, JJ., Burger, H., Boonstra, AM., et al.[2019]

In a study involving 10 Air Force pilots, modafinil (100 mg) significantly improved flight performance and mood during 37 hours of continuous wakefulness, maintaining accuracy at about 15-30% of baseline levels compared to a 60-100% decline in the placebo group.

Modafinil also reduced feelings of depression and anger while enhancing alertness and confidence, particularly after 24 to 32 hours without sleep, suggesting it could be a valuable tool for managing fatigue in military aviation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modafinil's effects on simulator performance and mood in pilots during 37 h without sleep. Caldwell, JA., Caldwell, JL., Smith, JK., et al.[2018]

In a study of 13 children with narcolepsy and idiopathic hypersomnia, modafinil significantly improved excessive daytime sleepiness, with 90% of parents reporting a favorable response after an average treatment duration of 15.6 months.

Modafinil was found to prolong mean sleep latency during multiple sleep latency tests, indicating its effectiveness, while showing a good safety profile with no significant changes in hematological and hepatic functions, although some children experienced exacerbation of preexisting conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modafinil in the treatment of excessive daytime sleepiness in children. Ivanenko, A., Tauman, R., Gozal, D.[2019]

Modafinil, a stimulant used for promoting wakefulness, can cause serious but rare dermatologic reactions, as demonstrated in a case where a patient developed a fixed drug eruption after just one dose.

The assessment using the Naranjo scale indicated that modafinil was a 'probable' cause of the adverse reaction, emphasizing the importance of monitoring for skin side effects in patients taking this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modafinil-induced Fixed Drug Eruption. Gaikwad, GV., Dhuri, CV.[2021]

In a study using an intravenous methamphetamine self-administration model, modafinil significantly reduced meth-seeking behavior in various reinstatement scenarios, particularly during meth-primed reinstatement.

These results suggest that modafinil could be an effective treatment for preventing relapse in individuals recovering from methamphetamine addiction, supporting its potential as a therapeutic agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modafinil effects on reinstatement of methamphetamine seeking in a rat model of relapse. Reichel, CM., See, RE.[2021]

Modafinil has a complex neurochemical profile that affects various brain systems, including catecholamines and serotonin, which may enhance cognitive functions like working memory and episodic memory in both healthy individuals and those with psychiatric disorders.

The medication is well-tolerated with a low incidence of adverse effects and a low potential for abuse, making it a promising option for treating cognitive dysfunction in conditions such as treatment-resistant depression and ADHD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modafinil: a review of neurochemical actions and effects on cognition. Minzenberg, MJ., Carter, CS.[2018]

In a study involving 16 healthy volunteers, modafinil significantly improved working memory performance, particularly in tasks requiring manipulation of information, without affecting overall speed or attentional control tasks.

The results suggest that modafinil enhances cognitive function related to working memory processes, especially in individuals who may initially perform at lower levels, indicating its potential as a cognitive enhancer in challenging tasks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of modafinil on working memory processes in humans. Müller, U., Steffenhagen, N., Regenthal, R., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Use of modafinil for the treatment of attention deficit/hyperactivity disorder. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Modafinil for the treatment of attention-deficit/hyperactivity disorder: A meta-analysis. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Modafinil as adjunctive therapy in depressed outpatients. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Modafinil in children and adolescents with attention-deficit/hyperactivity disorder: a preliminary 8-week, open-label study. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Effects of modafinil in children with attention-deficit/hyperactivity disorder: an open-label study. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of methylphenidate in 45 adults with attention-deficit/hyperactivity disorder. A randomized placebo-controlled double-blind cross-over trial. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Modafinil's effects on simulator performance and mood in pilots during 37 h without sleep. [2018]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Modafinil in the treatment of excessive daytime sleepiness in children. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Modafinil-induced Fixed Drug Eruption. [2021]

10. Germany pubmed.ncbi.nlm.nih.gov

Modafinil effects on reinstatement of methamphetamine seeking in a rat model of relapse. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Modafinil: a review of neurochemical actions and effects on cognition. [2018]

12. Germany pubmed.ncbi.nlm.nih.gov

Effects of modafinil on working memory processes in humans. [2022]