Modafinil for Attention Deficits

(LC Trial)

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests modafinil, a drug that may enhance attention and focus, by examining its effects on a brain region involved in attention and cognitive function. Researchers aim to compare modafinil's impact on brain activity with that of a placebo (a substance with no active drug). The trial is open to healthy adults without a history of schizophrenia, heart problems, or severe drug or alcohol use in the past five years. Participants should also be comfortable with MRI scans and not have metal implants or claustrophobia. As a Phase 4 trial, this research seeks to understand how the already FDA-approved and effective modafinil benefits more patients.

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 is the safety track record for Modafinil?

Research shows that modafinil is generally safe for people. The FDA has approved it for treating conditions like narcolepsy and other sleep disorders, confirming its safety for these uses. However, modafinil might cause mild side effects, such as headaches, nausea, or dizziness.

Modafinil should not be used during pregnancy, as it may harm the baby. People with severe liver problems might need to take lower doses. Although modafinil has a lower risk of abuse compared to other stimulants, it should always be used under a doctor's supervision. Overall, research suggests that modafinil is well-tolerated by most people when used correctly. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for attention deficits, which often include stimulant medications like methylphenidate or amphetamines, Modafinil works differently by targeting the brain's wakefulness pathways. Researchers are excited about Modafinil because it has a unique mechanism of action that promotes alertness without the jitteriness often associated with traditional stimulants. Additionally, Modafinil is known for having a lower potential for abuse, making it a promising alternative for managing attention deficits.

What is the effectiveness track record for Modafinil in treating attention deficits?

Research shows that modafinil, which participants in this trial may receive, can improve focus and thinking skills. Studies have found that it enhances decision-making and planning, although it might not affect short-term memory. It increases alertness in people who are not tired and helps them stay awake. Both healthy adults and those with cognitive difficulties have demonstrated modafinil's effects on short-term memory and impulse control. This evidence suggests that modafinil could effectively help with attention problems. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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 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]

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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3800148/

The neurobiology of modafinil as an enhancer of cognitive ... However, positive trends in several result measures suggest that medications that improve cognitive function, like MOD or R-MOD, may be beneficial for treatment ...

2. ox.ac.uk ox.ac.uk/news/2015-08-20-review-%E2%80%98smart-drug%E2%80%99-shows-modafinil-does-enhance-cognition

Review of 'smart drug' shows modafinil does enhance ... Modafinil made no difference to working memory, or flexibility of thought, but did improve decision-making and planning. Very encouragingly, the ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0924977X20302145

How effective are pharmaceuticals for cognitive ... The authors found that MPH improved memory, whereas modafinil only improved attention in non-sleep deprived individuals (but had a greater effect on wakefulness ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/15121488/

Modafinil improves cognition and response inhibition in ... Modafinil produced a similar pattern of cognitive enhancement to that observed in healthy adults, with improvements on tests of short-term memory span, visual ...

5. en.wikipedia.org en.wikipedia.org/wiki/Modafinil

Modafinil Research on the cognitive enhancement effects of modafinil in non-sleep deprived individuals has yielded mixed results, with some studies suggesting modest ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2010/020717s030s034s036lbl.pdf

PROVIGIL® (modafinil) Tablets [C-IV] Rx Only DESCRIPTION The dose of PROVIGIL should be reduced in patients with severe hepatic impairment (See PRECAUTIONS and. DOSAGE AND ADMINISTRATION). CLINICAL TRIALS. The ...

7. go.drugbank.com go.drugbank.com/drugs/DB00745

Modafinil: Uses, Interactions, Mechanism of Action Modafinil activates glutamatergic circuits while inhibiting GABA. Modafinil is thought to have less potential for abuse than other stimulants.

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0161813X2030036X

Memory improvement by modafinil at cost of metabolic ... Modafinil overuse may pose adverse metabolic repercussions. Modafinil initiated hyperglycaemia and dyslipidaemia in rats. It attenuated oxidative stress and ...