Focused Ultrasound for Behavioral Health (VANTUS)
Bayesian-Optimized Dose-Finding of ATTN201 Focused Ultrasound for Behavioral Health
This is a double-blind, within-participant crossover, multi-site dose-finding study evaluating the safety, feasibility, and preliminary efficacy of repeated low-intensity focused ultrasound (LIFU) stimulation using the ATTN201 device across seven candidate deep-brain targets in adults with subsyndromal-to-moderate depression, anxiety, or obsessive-compulsive disorder. Every session delivers active ATTN201 stimulation; there is no sham or placebo condition. Participants and the on-site study staff who deliver stimulation and administer the clinical scales are blinded to the brain target and to the stimulation parameters assigned for each session by a constrained Bayesian optimization algorithm.
Visão geral do estudo
Status
Intervenção / Tratamento
Descrição detalhada
Following a remote pre-screen and an in-person screening/baseline visit (Visit 0), at which informed consent is obtained, eligibility is confirmed, baseline clinical scales are administered, optional biospecimens are collected from participants who consent to them, a multi-sequence brain MRI is acquired for targeting, and monitoring devices are fitted, each participant receives between 3 and 10 ATTN201 stimulation sessions spaced approximately 7 days apart. Each stimulation visit serves as the pre-stimulation baseline for that session, the 1-week post-stimulation measurement for the prior session, and the 2-week post-stimulation measurement for the session before that. A platform-administered scale battery at day 7 after the last stimulation captures the 1-week measurement for the final session; a remote final treatment-period follow-up approximately 2 weeks after the last stimulation captures the 2-week measurement. A remote 3-month post-treatment check-in captures durability and any delayed adverse events.
The trial uses a two-stage architecture. In Stage 1, visits are allocated across all seven candidate targets. After approximately 300 visits, the Sponsor and ARPA-H convene a joint review and select 3-5 targets for continued Bayesian optimization in Stage 2.
Monitoring during enrollment includes validated clinical scales (PHQ-9, GAD-7, OCI-R) at baseline, before each stimulation visit, at the final treatment-period follow-up, and at the 3-month follow-up; transdiagnostic visual analog scales, a morning sleep diary, and brief voice recordings prompted through the Attune platform during monitoring blocks; optional nightly ambulatory EEG; and a smart watch worn from Visit 0 through device return. All scheduled platform prompts are voluntary at the individual-prompt level.
Blinding: A single on-site research associate positions the device, runs the stimulation session, and administers participant-facing assessments, and is blinded to the brain target and parameter combination; this individual occupies both the care provider and the outcomes assessor role. The stimulation condition is selected by the Bayesian optimization algorithm and pushed to the device as a sealed session. The Lead Principal Investigator and the optimization team are unblinded as required to operate the adaptive design and do not deliver stimulation or administer participant-facing assessments. The independent Medical Monitors and the Data Safety and Monitoring Board receive unblinded safety data.
Tipo de estudo
Inscrição (Estimado)
Estágio
- Não aplicável
Contactos e Locais
Contato de estudo
- Nome: Keith Murphy, PhD
- Número de telefone: 415-658-7001
- E-mail: outreach@attuneneuro.com
Locais de estudo
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California
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San Francisco, California, Estados Unidos, 94107
- Ainda não está recrutando
- Attune Neurosciences, Inc.
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San Francisco, California, Estados Unidos, 94107
- Recrutamento
- Attune, San Francisco Clinical Research Center
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Contato:
- Keith Murphy, PhD
- Número de telefone: 4156587001
- E-mail: outreach@attuneneuro.com
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Investigador principal:
- Keith Murphy, PhD
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-
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
- Be between 22 and 80 years of age (inclusive) on the day of signing informed consent.
- Have at least one of the following at screening: PHQ-9 total score 5-16 (depression), GAD-7 total score 5-14 (anxiety), or OCI-R total score 14-27 (obsessive-compulsive disorder).
- If currently taking psychiatric medication, have been on the same stable dose(s) for at least 4 weeks prior to screening and be willing to maintain the regimen throughout the treatment period.
- Be able and willing to undergo a multi-sequence cranial MRI.
- Be willing to use the ATTN201 device during stimulation visits and to attempt use of monitoring devices (optional ambulatory EEG system, smart watch) during the pre- and post-stimulation monitoring blocks; use of the optional ambulatory EEG system does not affect eligibility.
- Sign the informed consent form, in accordance with local requirements, after the scope and nature of the investigation have been explained to the participant, and before any screening assessments.
- Be able to speak, read, and understand English.
- Be able to use a smartphone and the Attune platform.
- Possess the ability to respond verbally to questions, follow instructions, and complete study assessments.
- Be able to adhere to the treatment protocol and visit schedules through the 3-month post-treatment follow-up.
- Be judged by the investigator as likely to comply with study procedures and willing to participate in the entirety of the study.
- Be determined by the investigator to be medically stable at baseline as assessed by medical history and non-significant clinical results of a vital signs examination.
- Male participants must ensure a condom is used for all sexual intercourse and follow acceptable methods of contraception for their female partner for the entire duration of the study and for 90 days after the final study visit. Male participants should not father a child or donate sperm during this same period.
- Female participants who are sexually active agree to use two methods of contraception for the duration of the study and for 30 days after the final study visit, or not be of childbearing potential as indicated by natural menopause (≥12 consecutive months of spontaneous amenorrhea), hysterectomy, bilateral tubal ligation, bilateral oophorectomy (with or without hysterectomy) more than 6 weeks prior to screening, or a vasectomized partner with documented absence of sperm.
Exclusion Criteria:
- Columbia Suicide Severity Rating Scale (C-SSRS) score ≥ 3 (ideation with intent, with or without plan) at screening.
- Any suicide attempt within the past 12 months.
- Any change in psychiatric medication (start, stop, or dose change) within 4 weeks prior to screening.
- Has an unstable or severe medical or psychiatric condition that, in the investigator's judgment, would pose a safety risk to the participant or prevent completion of study procedures. Stable comorbid conditions (e.g., treated depression, anxiety, OCD, insomnia) within the protocol-specified score windows are permitted.
- Has an active, unstable substance use disorder including alcohol use disorder in the past 6 months (except for caffeine and nicotine). Participants on stable medication-assisted treatment (e.g., buprenorphine, methadone, naltrexone) for at least 6 months are eligible.
- Has a history of moderate-to-severe traumatic brain injury, or mild traumatic brain injury within the past 12 months.
- Has a history of seizure disorder or epilepsy, or any structural CNS lesion known to lower seizure threshold.
- Has any contraindications for completing a brain MRI scan (e.g., pacemaker, ferromagnetic implants).
- Body mass index (BMI) greater than 40 kg/m².
- Is pregnant, is attempting to become pregnant, or is nursing.
- Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is an investigational site or Sponsor staff member directly involved with this trial.
- Has a known allergy or sensitivity to ultrasound gel, silicone, or adhesive materials used in monitoring devices.
- Has an active skin condition at sensor placement sites that would prevent device wear.
- Has received an investigational drug or device in another clinical study within 30 days before screening
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Não randomizado
- Modelo Intervencional: Atribuição cruzada
- Mascaramento: Triplo
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: Basolateral amygdala (BLA)
ATTN201 head-worn low-intensity focused ultrasound delivered to the basolateral amygdala (BLA). Sessions at which the constrained Bayesian optimization algorithm assigns this target; stimulation parameters (pulse repetition frequency, duty cycle, target pressure) vary within the ITRUSST-bounded search space. Participants may cross over to other target arms at subsequent sessions. |
ATTN201 head-worn focused ultrasound |
|
Experimental: Dorsal anterior cingulate cortex (dACC)
ATTN201 head-worn low-intensity focused ultrasound delivered to the dorsal anterior cingulate cortex (dACC). Sessions at which the constrained Bayesian optimization algorithm assigns this target; stimulation parameters (pulse repetition frequency, duty cycle, target pressure) vary within the ITRUSST-bounded search space. Participants may cross over to other target arms at subsequent sessions. |
ATTN201 head-worn focused ultrasound |
|
Experimental: Anterior limb of internal capsule (ALIC)
ATTN201 head-worn low-intensity focused ultrasound delivered to the anterior limb of the internal capsule (ALIC). Sessions at which the constrained Bayesian optimization algorithm assigns this target; stimulation parameters (pulse repetition frequency, duty cycle, target pressure) vary within the ITRUSST-bounded search space. Participants may cross over to other target arms at subsequent sessions. |
ATTN201 head-worn focused ultrasound |
|
Experimental: Centromedian nucleus of thalamus (CMN)
ATTN201 head-worn low-intensity focused ultrasound delivered to the centromedian nucleus of the thalamus (CMN). Sessions at which the constrained Bayesian optimization algorithm assigns this target; stimulation parameters (pulse repetition frequency, duty cycle, target pressure) vary within the ITRUSST-bounded search space. Participants may cross over to other target arms at subsequent sessions. |
ATTN201 head-worn focused ultrasound |
|
Experimental: Rostral zona incerta (rZi)
ATTN201 head-worn low-intensity focused ultrasound delivered to the rostral zona incerta (rZi). Sessions at which the constrained Bayesian optimization algorithm assigns this target; stimulation parameters (pulse repetition frequency, duty cycle, target pressure) vary within the ITRUSST-bounded search space. Participants may cross over to other target arms at subsequent sessions. |
ATTN201 head-worn focused ultrasound |
|
Experimental: Subthalamic nucleus (STN)
ATTN201 head-worn low-intensity focused ultrasound delivered to the subthalamic nucleus (STN). Sessions at which the constrained Bayesian optimization algorithm assigns this target; stimulation parameters (pulse repetition frequency, duty cycle, target pressure) vary within the ITRUSST-bounded search space. Participants may cross over to other target arms at subsequent sessions. |
ATTN201 head-worn focused ultrasound |
|
Experimental: Anterior nucleus of thalamus (ANT)
ATTN201 head-worn low-intensity focused ultrasound delivered to the anterior nucleus of the thalamus (ANT). Sessions at which the constrained Bayesian optimization algorithm assigns this target; stimulation parameters (pulse repetition frequency, duty cycle, target pressure) vary within the ITRUSST-bounded search space. Participants may cross over to other target arms at subsequent sessions. |
ATTN201 head-worn focused ultrasound |
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Patient-specific transdiagnostic score (TDx) at 1 week after stimulation
Prazo: 1 week after each stimulation session
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TDx measured 1 week after each stimulation session. The TDx is a severity-weighted composite of normalized improvement on PHQ-9, GAD-7, and OCI-R; higher TDx indicates greater improvement. |
1 week after each stimulation session
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Patient-specific transdiagnostic score (TDx) at 2 weeks after stimulation
Prazo: 2 weeks after each stimulation session
|
TDx measured 2 weeks after each stimulation session. The TDx is a severity-weighted composite of normalized improvement on PHQ-9, GAD-7, and OCI-R; higher TDx indicates greater improvement. |
2 weeks after each stimulation session
|
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Posterior mean transdiagnostic score (TDx) at the best stimulation parameter set for each brain target
Prazo: At study completion, up to 19 months
|
Posterior mean TDx, from a Gaussian process model fit for each brain target, at the stimulation parameter set that maximizes it. TDx is a severity-weighted composite of normalized improvement on PHQ-9, GAD-7, and OCI-R; higher TDx indicates greater improvement. |
At study completion, up to 19 months
|
|
Change from pre-stimulation baseline in PHQ-9 total score
Prazo: Pre-stimulation baseline, 1 week after stimulation, and 2 weeks after stimulation
|
Change from the local pre-stimulation baseline in Patient Health Questionnaire-9 (PHQ-9) total score. The PHQ-9 is a 9-item self-report measure of depression severity over the preceding 2 weeks. Total score range is 0 to 27; higher scores indicate greater depression severity. A negative change score indicates improvement. |
Pre-stimulation baseline, 1 week after stimulation, and 2 weeks after stimulation
|
|
Change from pre-stimulation baseline in GAD-7 total score
Prazo: Pre-stimulation baseline, 1 week after stimulation, and 2 weeks after stimulation
|
Change from the local pre-stimulation baseline in Generalized Anxiety Disorder-7 (GAD-7) total score. The GAD-7 is a 7-item self-report measure of anxiety severity over the preceding 2 weeks. Total score range is 0 to 21; higher scores indicate greater anxiety severity. A negative change score indicates improvement. |
Pre-stimulation baseline, 1 week after stimulation, and 2 weeks after stimulation
|
|
Change from pre-stimulation baseline in OCI-R total score
Prazo: Pre-stimulation baseline, 1 week after stimulation, and 2 weeks after stimulation
|
Change from the local pre-stimulation baseline in Obsessive-Compulsive Inventory-Revised (OCI-R) total score. The OCI-R is an 18-item self-report measure of distress associated with obsessive-compulsive symptoms. Total score range is 0 to 72; higher scores indicate greater symptom severity. A negative change score indicates improvement. |
Pre-stimulation baseline, 1 week after stimulation, and 2 weeks after stimulation
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Mood visual analog scale (VAS) score
Prazo: Daily from Day 1 through Day 7 after each stimulation session
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Self-rated mood on a 0-100 continuous VAS administered through the Attune platform; higher scores indicate better mood. |
Daily from Day 1 through Day 7 after each stimulation session
|
|
Arousal visual analog scale (VAS) score
Prazo: Daily from Day 1 through Day 7 after each stimulation session
|
Self-rated arousal on a 0-100 continuous VAS administered through the Attune platform; higher scores indicate greater arousal. |
Daily from Day 1 through Day 7 after each stimulation session
|
|
Sleepiness visual analog scale (VAS) score
Prazo: Daily from Day 1 through Day 7 after each stimulation session
|
Self-rated sleepiness on a 0-100 continuous VAS administered through the Attune platform; higher scores indicate greater sleepiness. |
Daily from Day 1 through Day 7 after each stimulation session
|
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Anxiety symptom visual analog scale (VAS) score
Prazo: Daily from Day 1 through Day 7 after each stimulation session
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Self-rated current anxiety symptoms on a 0-100 continuous VAS administered through the Attune platform; higher scores indicate greater anxiety. |
Daily from Day 1 through Day 7 after each stimulation session
|
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Obsessive-compulsive symptom visual analog scale (VAS) score
Prazo: Daily from Day 1 through Day 7 after each stimulation session
|
Self-rated current obsessive-compulsive symptoms on a 0-100 continuous VAS administered through the Attune platform; higher scores indicate greater symptom severity. |
Daily from Day 1 through Day 7 after each stimulation session
|
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Depression symptom visual analog scale (VAS) score
Prazo: Daily from Day 1 through Day 7 after each stimulation session
|
Self-rated current depression symptoms on a 0-100 continuous VAS administered through the Attune platform; higher scores indicate greater symptom severity. |
Daily from Day 1 through Day 7 after each stimulation session
|
|
Prefrontal EEG delta band spectral power
Prazo: Nightly from Day 1 through Day 7 after each stimulation session
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Absolute spectral power in the delta band from nightly two-channel prefrontal ambulatory EEG recordings, among participants who elect optional EEG monitoring. |
Nightly from Day 1 through Day 7 after each stimulation session
|
|
Prefrontal EEG theta band spectral power
Prazo: Nightly from Day 1 through Day 7 after each stimulation session
|
Absolute spectral power in the theta band from nightly two-channel prefrontal ambulatory EEG recordings, among participants who elect optional EEG monitoring. |
Nightly from Day 1 through Day 7 after each stimulation session
|
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Prefrontal EEG alpha band spectral power
Prazo: Nightly from Day 1 through Day 7 after each stimulation session
|
Absolute spectral power in the alpha band from nightly two-channel prefrontal ambulatory EEG recordings, among participants who elect optional EEG monitoring. |
Nightly from Day 1 through Day 7 after each stimulation session
|
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Prefrontal EEG beta band spectral power
Prazo: Nightly from Day 1 through Day 7 after each stimulation session
|
Absolute spectral power in the beta band from nightly two-channel prefrontal ambulatory EEG recordings, among participants who elect optional EEG monitoring. |
Nightly from Day 1 through Day 7 after each stimulation session
|
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Prefrontal EEG gamma band spectral power
Prazo: Nightly from Day 1 through Day 7 after each stimulation session
|
Absolute spectral power in the gamma band from nightly two-channel prefrontal ambulatory EEG recordings, among participants who elect optional EEG monitoring. |
Nightly from Day 1 through Day 7 after each stimulation session
|
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EEG-derived sleep efficiency
Prazo: Nightly from Day 1 through Day 7 after each stimulation session
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Sleep efficiency (percentage of time in bed spent asleep) derived by automated sleep staging of nightly two-channel prefrontal ambulatory EEG recordings, among participants who elect optional EEG monitoring. |
Nightly from Day 1 through Day 7 after each stimulation session
|
|
Smart-watch-derived heart rate variability
Prazo: Daily from Day 1 through Day 7 after each stimulation session
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Daily heart rate variability (milliseconds) recorded by the study smart watch. |
Daily from Day 1 through Day 7 after each stimulation session
|
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Smart-watch-derived daily step count
Prazo: Daily from Day 1 through Day 7 after each stimulation session
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Daily step count (actigraphy) recorded by the study smart watch. |
Daily from Day 1 through Day 7 after each stimulation session
|
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Smart-watch-derived sleep duration
Prazo: Nightly from Day 1 through Day 7 after each stimulation session
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Nightly total sleep duration (minutes) recorded by the study smart watch. |
Nightly from Day 1 through Day 7 after each stimulation session
|
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Life-space mobility
Prazo: Daily from Day 1 through Day 7 after each stimulation session
|
Daily life-space mobility (maximum distance from home, kilometers) derived from de-identified GPS collected by the optional Beiwe research application on the participant's smartphone. |
Daily from Day 1 through Day 7 after each stimulation session
|
|
Patient-specific transdiagnostic score (TDx) at 1 week after stimulation, by primary indication
Prazo: 1 week after each stimulation session
|
TDx measured 1 week after each stimulation session, summarized separately for participants whose primary indication is depression, anxiety, obsessive-compulsive disorder, or comorbid. TDx is a severity-weighted composite of normalized improvement on PHQ-9, GAD-7, and OCI-R; higher TDx indicates greater improvement. |
1 week after each stimulation session
|
Colaboradores e Investigadores
Patrocinador
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- Pro00095585
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Descrição do plano IPD
De-identified individual participant data will be deposited into the ARPA-H designated data repository as required by the funded ARPA-H EVIDENT program. Deposited data include clinical outcome measures (PHQ-9, GAD-7, OCI-R, PROMIS Sleep Disturbance 8a, PROMIS Sleep-Related Impairment 8a, DASS-8, Brief Resilience Scale, Flourishing Scale, and transdiagnostic visual analog scales), delivered stimulation parameters, EEG-derived and wearable-derived biomarker measures, platform-derived measures, relevant metadata, and optional baseline dried blood spot and saliva biospecimens where collected. Participant identifiers are not included in deposited datasets.
Prazo de Compartilhamento de IPD
Deposits occur on rolling quarterly delivery cycles beginning after enrollment of the first participant and continuing through study completion. Deposited data remain available thereafter under the retention terms of the ARPA-H designated data repository.
Critérios de acesso de compartilhamento IPD
Access is governed by the data access procedures of the ARPA-H designated data repository. Requests for deposited data are made to the repository rather than to the sponsor.
Tipo de informação de suporte de compartilhamento de IPD
- PROTOCOLO DE ESTUDO
- SEIVA
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