Clinical trial NCT06967857: Clinical Trial to Investigate the Safety and Efficacy of Two Dexamfetamine Sulfate Formulations in Adults With ADHD and Moderate to Severe Depression
Official title: Randomized, Placebo-controlled Clinical Trial to Investigate the Safety and Efficacy of Two Dexamfetamine Sulfate Formulations in Adults With ADHD and Moderate to Severe Depression (DEXAD)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Attention-Deficit/Hyperactivity Disorder (ADHD)
Depression - Major Depressive Disorder
Keywords: ADHD
Depression
Adults
Lead sponsor: Fraunhofer Institute for Translational Medicine and Pharmacology ITMP
Sponsor class: OTHER
First posted: 2025-05-13
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomised, double blind
Primary purpose: TREATMENT

Brief summary: The indication of attention-deficit/hyperactivity disorder (ADHD) to be examined often occurs with other psychiatric disorders, and the majority of adults with ADHD have at least one psychiatric comorbidity in their lives. Depression is one of the most common comorbidities in patients with ADHD. The prevalence of comorbid depression in adults with ADHD is estimated to be as high as 50%.

There is evidence that stimulants such as dexamfetamine and methylphenidate lead to an improvement in sustained focused attention, working memory, and a variety of cognitive processes in the prefrontal cortex (PFC). In combination with the pharmacological effects of stimulants, such as the inhibition of monoamine oxidase, the increase in the concentration of noradrenaline in the PFC and dopamine in the striatum, dexamfetamine and methylphenidate could improve the treatment of depression in patients with major depressive disorder and comorbid ADHD.

This clinical trial will evaluate the safety and efficacy of DEX in two different formulations compared to placebo in adults with ADHD and moderate to severe depression. To ensure double blinding of the treatment, placebo will be administered in the form of tablets and capsules.


Eligibility criteria: Inclusion Criteria:

1. Diagnosis of attention deficit / hyperactivity disorder (ADHD) (according to DSM-5 (fifth version of Diagnostic and Statistical Manual of Mental Disorders) or ICD (International Statistical Classification Of Diseases And Related Health Problems) guidelines) which started in childhood (at the age of \<12 years)
2. Patient has a minimum ADHS-Diagnostische Checkliste-Q (ADHS-DC) total score of 32 at baseline (Visit (V) 0)
3. Moderate to severe depression according to ICD-10 (depressive episode: Code F32; recurrent depressive disorder: Code F33) and with a Montgomery-Åsberg Depression Rating Scale (MADRS) score of \>20 at baseline (V0)
4. CGI-S ≥ 4 at baseline (V0)
5. Patients receiving selective serotonin reuptake inhibitors (SSRIs) or Serotonin-norepinephrine reuptake inhibitors (SNRIs) (stable doses within the last 2 weeks before inclusion) (≤40 mg (es)citalopram, 50-200 mg sertraline, 75 - 300 mg venlafaxine extended release)
6. Male or female patients ≥ 18 years and ≤ 65 at time of enrolment
7. Patients with QTc interval within normal ranges (≤470 ms in males and ≤480 ms in females)
8. Patient is either free of stimulant medication or who, after discussion with his / her treating physician, is able and willing to discontinue the current psychotropic medication(s) for treatment of ADHD symptoms (specifically, methylphenidate, lisdexamfetamine, guanfacine or atomoxetine or any other medication approved for the treatment of ADHD) ) for the duration of the study, as well as is able and willing to discontinue all relevant co-medication according to exclusion criterion no. 20a-s for comorbid conditions during the clinical trial, if applicable
9. Written informed consent and data protection declaration obtained prior to the initiation of any protocol required procedures
10. Willing and able to comply to study procedures and study protocol

Exclusion Criteria:

1. Current or a history of severe co-morbid symptoms such as psychotic symptoms, schizophrenia, bipolar disorders or manic episodes
2. Current or recent history of substance abuse disorder within the last 6 months of clinical trial entry
3. Patients with body mass index (BMI) \< 18.5 kg/m² or \>35 kg/m²
4. History of serotonin syndrome events
5. History of seizures or use of anticonvulsant medication
6. Any other uncontrolled psychiatric condition that requires medication or may interfere with trial participation
7. Known symptomatic cardiovascular disease including structural abnormalities, moderate and severe hypertension (systolic blood pressure ≥160 mmHg, diastolic blood pressure ≥100 mmHg), heart failure, myocardial infarction, arterial occlusive disease, angina, haemodynamically significant congenital heart disease, cardiomyopathies, potentially life-threatening arrhythmias and channelopathies (diseases caused by ion channel dysfunction)
8. Significant, in the discretion of the investigator, hepatic, gastrointestinal, renal, haematological or oncologic disorder
9. Diagnosis of glaucoma, hyperthyroidism, pheochromocytoma or porphyria
10. Diagnosis or family history of Tourette's syndrome or dystonia
11. Pre-existing cerebrovascular disorders such as cerebral aneurysm, vascular abnormalities including vasculitis or stroke
12. Immunodeficiency disorders (e.g. organ transplantation, Human Immunodeficiency Virus (HIV) infection)
13. Known hypersensitivity to any of the ingredients of the trial medication, e.g. patients with known rare hereditary problems of fructose intolerance
14. Males or females of reproductive potential not willing to use effective contraception (defined as PEARL index \<1 - e.g. contraceptive pill, intrauterine device (IUD)) during the study period (Screening to Follow-up)
15. Pregnancy and lactation
16. Participation in another interventional clinical trial during the trial and within the previous 30 days prior to trial start
17. Patients who are institutionalised by court order or regulatory action
18. Patients, who are members of the staff of the trial centre, staff of the sponsor or involved Clinical Research Organisation (CRO), the investigator him- / herself or close relatives of the investigator
19. Legal incapacity and/ or other circumstances rendering the patient unable to understand the nature, scope and possible impact of the clinical trial
20. Current use of and use within the last 2 weeks before inclusion due to possible interactions with stimulants or SSRIs/SNRIs and possible resulting or expected side effects:

    1. Antipsychotics (such as chlorpromazine, haloperidol, thioridazine; except for quetiapine up to 100mg/day)
    2. SSRIs and SNRIs daily doses of \>40 mg (es)citalopram, \>200 mg sertraline, \>300 mg venlafaxine extended release
    3. Monoamine oxidase inhibitors (MAO) inhibitors
    4. tricyclic antidepressants
    5. benzodiazepines (including Z-drugs)
    6. atypical antidepressants (with an exception for daily doses of 100-300 mg trazodone)
    7. Dopamine reuptake inhibitors (special restriction for bupropion)
    8. antiarrhythmics (Class IA and III)
    9. antibiotics (in particular macrolides and fluoroquinolones, linezolid)
    10. opioids
    11. hydroxychloroquine, chloroquine
    12. ketoconazole
    13. acetylsalicylic acid (dose up to 300 mg allowed)
    14. diphenhydramine
    15. apixaban
    16. metoprolol
    17. pregabalin
    18. budesonide / formoterol
    19. albuterol / salbutamol

Primary outcomes:
measure: Incidence of adverse events (AE) in the active treatment groups compared to the placebo until V6
timeFrame: from enrollment to the end of study at week 17
Secondary outcomes:
measure: Incidence of adverse events (AE) until V5
timeFrame: Start with enrollment until end of treatment at Week 16
measure: Proportion of patients with at least one AE until V5
timeFrame: through study treatment (up to 16 weeks)
measure: Proportion of patients with at least one AE until end of study
timeFrame: from baseline until end of study at week 17
measure: Number of AE until V5
timeFrame: through study treatment (up to 16 weeks)
measure: Number of AE until V5 and until end of study
timeFrame: from baseline until end of study at week 17
measure: Number of AE/SAE during the study period
timeFrame: through study treatment (up to 16 weeks)
measure: number of patients with AE/SAE by type during study period
timeFrame: through study treatment (up to 16 weeks)
measure: proportion of patients with AE/SAE by type during study period
timeFrame: through study treatment (up to 16 weeks)
measure: number of patients with AE/SAE by severity (mild, moderate, severe) during study period
timeFrame: through study treatment (up to 16 weeks)
measure: proportion of patients with AE/SAE by severity (mild, moderate, severe) during study period
timeFrame: through study treatment (up to 16 weeks)
measure: number of patients with AE/SAE by relatedness to treatment during study period
timeFrame: through study treatment (up to 16 weeks)
measure: proportion of patients with AE/SAE by relatedness to treatment during study period
timeFrame: from enrollment to the end of study at week 17
measure: Score of clinical global impression (CGI) Efficacy index by investigator at Visit 5
timeFrame: 16 weeks after treatment start
measure: MADRS suicidal ideation score for all available visits (screening to Visit 5)
timeFrame: from enrollment to the end of treatment (up to week 16)
measure: MADRS suicidal ideation score for all available visits
timeFrame: from enrollment to end of titration at week 4 (V1)
measure: MADRS suicidal ideation score for all available visits
timeFrame: from enrollment to week 7 (V2)
measure: MADRS suicidal ideation score change to BL/V0 (on V1)
timeFrame: from baseline to end of treatment titration phase at 4 weeks
measure: MADRS suicidal ideation score change to BL/V0 (on V5)
timeFrame: from treatment start to end of treatment at 16 weeks
measure: MADRS suicidal ideation score for all available visits
timeFrame: from enrollment to 10 weeks (V3)
measure: MADRS suicidal ideation score for all available visits
timeFrame: from enrollment to 13 weeks (V4)
measure: MADRS suicidal ideation score for all available visits (screening to visit 5)
timeFrame: from enrollment to 16 weeks (V5)
measure: Rate of patients with score 1-3 in CGI-I at V5
timeFrame: from baseline to 16 weeks (V5)
measure: Absolute scores categories of CGI-I at all available visits
timeFrame: from end of treatment titration phase at 4 weeks (V1) to week 7 (V2)
measure: Absolute scores categories of CGI-I at all available visits (V1 to V2)
timeFrame: from end of titration phase (week 4) to 7 weeks (V2)
measure: Absolute scores categories of CGI-I at all available visits (V1 to V3)
timeFrame: from end of titration phase (week 4) to 10 weeks (V3)
measure: Absolute scores categories of CGI-I at all available visits (V1 to V4)
timeFrame: from end of titration phase (week 4) to 13 weeks (V4)
measure: Absolute scores categories of CGI-I at all available visits (V1 to V5)
timeFrame: from end of titration phase (week 4) to end of treatment at 16 weeks (V5)
measure: Numbers and percentages of patients with (1) decreased, (2) maintained and (3) increased CGI-S at V5 compared to BL/V0
timeFrame: from baseline to end of treatment at 16 weeks (V5)
measure: Shift table of CGI-S score categories at BL/V0
timeFrame: at baseline
measure: Shift table of CGI-S score categories at V1
timeFrame: from baseline to end of treatment titration phase at 4 weeks (V1)
measure: Shift table of CGI-S score categories at V5
timeFrame: from baseline to end of treatment at 16 weeks (V5)
measure: Absolute score categories of CGI-S at V0
timeFrame: at baseline (V0)
measure: Absolute score categories of CGI-S at V0 to V2
timeFrame: from baseline to 7 weeks (V2)
measure: Absolute score categories of CGI-S at V0 to V1
timeFrame: from baseline to end of treatment titration phase at 4 weeks (V1)
measure: Absolute score categories of CGI-S at V0 to V3
timeFrame: from baseline to 10 weeks (V3)
measure: Absolute score categories of CGI-S at V0 to V4
timeFrame: from baseline to 13 weeks (V4)
measure: Absolute score categories of CGI-S at V0 to V5
timeFrame: from baseline to end of treatment at 16 weeks (V5)
measure: MADRS total score (range 0-60) for all available visits (SCR to V5)
timeFrame: Screening until end of treatment at week 16 (V5)
measure: MADRS total score (range 0-60) MADRS total score (range 0-60) change to BL/V0 (at V5)
timeFrame: baseline until end of treatment at week 16 (V5)
measure: MADRS total score categorization by Müller et al. at BL/ V0
timeFrame: at baseline
measure: ADHS-DC-Q total score (range 0-66) for all available visits (SCR to V5)
timeFrame: Screening to end of treatment at week 16
measure: ADHS-DC-Q total score (range 0-66) change to BL/V0 (V1)
timeFrame: from baseline to end of titration at week 4 (V1)
measure: QIDS-SR-16 total score (range 0-27) for all available visits (V0 to V5)
timeFrame: baseline to end of treatment at 16 weeks
measure: QIDS-SR-16 total score (range 0-27) change to BL/V0 (V5)
timeFrame: from baseline to end of treatment at week 16 (V5)
measure: Mean dose intake from V1 to V5 per treatment group
timeFrame: from end of titration (week 4, V1) until end of treatment at week 16
measure: Mean dose intake compared to planned dose after titration phase (for study period V1 to V5) per treatment group
timeFrame: end of titration phase (visit 1) 4 weeks after baseline until end of treatment at week 16 (12 weeks after titration phase)
measure: Proportion of patients with less than 80% of planned dose intake (for study period V1 to V5) per treatment group
timeFrame: visit 1 (4 weeks after baseline) until end of treatment at week 16
measure: Number of patients by dosage group at V1 and V2
timeFrame: at visit 1 (4 weeks after baseline) and at visit 2 (3 weeks after visit 1)
measure: Proportion of patients by dosage group at V1 and V2
timeFrame: at visit 1 (4 weeks after baseline) and at visit 2 (3 weeks after visit 1)
measure: Number of patients per treatment group that needed dose optimization of IMP in the optimal stable dose phase and type of optimization (e.g., downtitration)
timeFrame: end of titration phase (visit 1) 4 weeks after baseline until end of treatment at week 16 (12 weeks after titration phase)
measure: Proportion of patients per treatment group that needed dose optimization of IMP in the optimal stable dose phase and type of optimization (e.g., downtitration)
timeFrame: end of titration phase (visit 1) 4 weeks after baseline until end of treatment at week 16 (12 weeks after titration phase)
measure: Number of patients with early withdrawal from therapy due to adverse events
timeFrame: baseline until end of treatment at week 16 (12 weeks after end of titration phase)
measure: Number of patients with early withdrawal from therapy due to adverse events per treatment group
timeFrame: baseline until end of treatment at week 16 (12 weeks after end of titration phase)
measure: percentage of patients with early withdrawal from therapy due to adverse events in total
timeFrame: baseline until end of treatment at week 16 (12 weeks after end of titration phase)
measure: Percentage of patients with early withdrawal from therapy due to adverse events per treatment group
timeFrame: baseline until end of treatment at week 16 (12 weeks after end of titration phase)
measure: MADRS total score categorization by Müller et al. at BL/ V0, V1 and V5
timeFrame: at baseline, at end of titration phase (week 4) and at end of treatment (week 16, V5)
measure: MADRS total score (range 0-60) MADRS total score (range 0-60) change to BL/V0 (at V1)
timeFrame: baseline until end of titration phase at week 4 (V1)
measure: ADHS-DC-Q total score (range 0-66) change to BL/V0 (V1)
timeFrame: baseline until end of titration phase at week 4 (V1)
measure: ADHS-DC-Q total score (range 0-66) change to BL/V0 (to V5)
timeFrame: baseline until end of treatment at week 16 (V5)
measure: QIDS-SR-16 total score (range 0-27) change to BL/V0 (V1)
timeFrame: from baseline to end of titration (week 4, V1)
measure: MADRS suicidal ideation score for all available visits
timeFrame: from enrollment to baseline (start of treatment, V0)
Other outcomes:
Locations:
city: Frankfurt
country: Germany
facility: Department of Psychiatry, Psychosomatics and Psychotherapy University Hospital Frankfurt am Main - Goethe University
city: Leipzig
country: Germany
facility: University Leipzig, Department of Psychiatry and Psychotherapy
Study officials:
affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy University Hospital Frankfurt am Main - Goethe University
name: Andreas Reif, Prof. Dr. med.
role: STUDY_CHAIR
References: