Attenuated Psychosis SyndromeNCT02155699

Exercise and Markers of Medial Temporal Health in Youth At-risk for Psychosis

A study testing Exercise 1 and Exercise 2 in people with Attenuated Psychosis Syndrome, run by University of Colorado, Boulder at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 16 to 24 yearsHealthy volunteers can take part
Conditions the study is for: Attenuated Psychosis Syndrome
What is being tested?: Exercise 1 and Exercise 2
Type of treatment: Lifestyle or therapy programme
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 50 participants
Where: 1 siteUnited States
Study dates: Jul 2014to Jul 2022
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 16 to 24 years
All sexes
Healthy volunteers accepted
Child, Adult

Who may be able to join

age 16-24
no history of brain injury or neurological disease
no contraindications to exercise training (as assessed by a Clinical Translational Research Center CTRC physician)
no history or current treatment with antipsychotics
no contraindications for being in an magnetic resonance imaging scanner.
meet criteria for a prodromal syndrome based upon the Structure Interview for Prodromal Syndromes (SIPS) interview.

Who cannot join

people who are extremely claustrophobic
have a history of significant head injury
other physical disorder that could affect brain functioning
mental retardation
history of substance use disorder within 6 months of screening interview
have a psychotic disorder (at study entry) and/or have exhibited serious self-harm behaviors

Show all 10Show fewer

pregnant females
people who have contraindications to magnetic resonance (MR) scanning including intracranial, intraorbital or intraspinal metal, pacemakers, cochlear implants or other non-MR-compatible devices
inability of the subject or their parent/guardian to understand the informed consent document
meeting criteria for an Axis I psychotic disorder

Trial locations and contacts

1 site in 1 country.

United States1 site

ADAPT Program
Boulder, Colorado, 80309

Other trials in United States

About this study

Official title: Exercise and Markers of Medial Temporal Health in Youth at Ultra High-risk for Psychosis

The goal of this proposal is to test the feasibility and effectiveness of cardiovascular exercise in promoting brain health and improving related symptoms (e.g., hearing sounds that are not there, feeling emotionally detached from self and others), cognitive difficulties (troubles with memory and learning), and every day social-occupational functioning in youth at imminent risk for developing a psychotic disorder such as schizophrenia. Understanding how exercise may protect or improve the health of a brain area that is implicated as a major contributing factor to the onset of psychosis may lead to a path-breaking new intervention that does not suffer from many of the side effects, costs, and other barriers that characterize treatments that are currently available for this group. Because a significant portion of high-risk youth go on to develop a psychotic disorder in a short period, intervening at this stage may help to improve the clinical course and ultimately prevent the onset of a devastating and prevalent mental illness.

Read the detailed description

Accumulating evidence from the animal literature, healthy populations, and schizophrenia studies suggests that regular exercise positively affects integral functions such as neurogenesis, synaptic plasticity and cognition. Likewise, preliminary evidence suggests that aerobic activity has been associated with improved quality of life and a lower level of symptoms in patients with schizophrenia. Because exercise has been found to stimulate human medial temporal neurogenesis, and related abnormalities have been widely observed in studies of schizophrenia, physical activity may be in an important intervention. During the psychosis prodrome, a period immediately proceeding formal onset of psychotic disorders, adolescents experience subtle attenuated symptoms coupled with cognitive deterioration and a global decline in socio-occupational functioning and anywhere between 10-35% go on to transition to a psychotic disorder such as schizophrenia in a two-year period. Despite the promise of exercise interventions, and the critical role medial temporal lobe abnormalities play in etiological models of psychosis, there have been no experimental studies of aerobic exercise in ultra-high risk youth (UHR). Understanding the potential benefits of aerobic exercise in UHR youth is integral as the prodrome is a viable period of intervention in which considerable brain development is still occurring. Further, as there have been challenges associated with many of the available interventions, and an increasing level of potential found in neuroplasticity-based interventions, understanding the effect of exercise on respective brain-behavior holds considerable promise. Experimental research is sorely needed to determine if prescribed aerobic exercise can stimulate medial-temporal neurogenesis and ameliorate cognition and symptoms/functioning in this vital group. In the proposed study, an expert team of experienced prodromal and exercise investigators will follow a group of 15 UHR adolescent and young adults (ages 16-24) through a 12 week exercise trial to determine which level of exercise intensity/frequency is tolerable for participants and optimal for improving aerobic fitness (65% of VO2max and 2 sessions per week versus 85% intensity and 3 sessions per peek) and if improvements in aerobic fitness (i.e., VO2max, VO2peak, ventilatory threshold) are associated with increases in medial temporal structure volume (hippocampus and parahippocampal gyrus) and accompanying improvements in cognitive function (i.e., including tasks known to recruit heavily on medial temporal structures) as well as symptomatology and social/role functioning. If the benchmarks are met, this data will be used to streamline a three-year rater-blind controlled trial (15 UHR-exercise, 15 UHR waitlist-control) to determine the efficacy of the intervention in promoting medial temporal health as well as accompanying cognitive, clinical, and socio-occupational function improvement. Participants will be followed up to 24-months to determine if the intervention has an affect on clinical course and transition to psychosis. Taken together, this study is important for understanding the lessons necessary for planning a future large-scale trial, and has the potential to shed light on a promising new treatment for UHR youth.

Conditions: Attenuated Psychosis Syndrome
Being tested: Exercise 1, Exercise 2
Keywords: UHR, Remediation, Exercise, Intervention, Psychosis
Medical subject headings: Motor Activity, Psychotic Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Exercise 1Behavioural
65% of VO2max and 2 sessions per week
Exercise 2Behavioural
85% intensity and 3 sessions per peek

Study groups in NCT02155699
Study group	Role	What they receive
Exercise 1	Experimental	65% of V02 Max, 3x per week, 3 months Receives: Behavioral: Exercise 1
Exercise 2	Experimental	85% of VO2 Max, 2x per week, 3 months Receives: Behavioral: Exercise 2
Waitlist	No intervention	Waitlist (three months)

What is being measured

The primary outcome is the main question the study is designed to answer.

Brain Volume
Medial temporal structures (hippocampus and parahippocampal gyrus) will be delineated automatically using the FMRIB's Integrated Registration and Segmentation Tool algorithm within the FMRIB's Software Library (FSL) image-processing suite. Secondly, the structures will be evaluated with vertex analyses (assessing changes in shape post trial on a per-vertex basis), which will also be carried out utilizing FIRST. Shape/appearance models used in FIRST are constructed from manually segmented images provided by the Center for Morphometric Analysis (CMA, Boston). This approach is different from using a whole-structure summary measure like volume, as it allows visualization of the region of the shape that is changing as well as the type of shape change.
Measured: pre-trial, post-trial (3-months)

Secondary outcomes (1)

Working Memory Assessment
Working Memory Assessment - Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) battery working memory subscale - a higher score indicates working memory better performance. The Relational and Item-Specific Encoding task includes visual object representations of word stimuli. Subjects make a two-button "yes/no" response to indicate whether items in each pair had been presented "together."To prevent additional encoding of the relational object pairs the item recognition task precedes the associated recognition task. Higher scores reflect the familiarity and recollection performance as well as hit rates and false alarm rates following encoding - better performance. MATRICS Consensus Cognitive Battery working memory subscale using a t-score (0=population mean, standard deviation=10) and Relational and Item-Specific Encoding Task accuracy score in the RCT study using a task specific accuracy (d prime range; 0-100%).
Measured: pre-trial, post-trial (3-months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2014Jul 2022

First posted4 Jun 2014 (estimated)
Study startJul 2014
Primary completionJul 2022
Study completionJul 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (7)Papers the sponsor has linked to this study.
Other trials for Attenuated Psychosis SyndromeStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Single group
Masking: Single blind
Who is masked: Outcomes assessor
Enrolment: 50 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02155699
Sponsor's protocol ID: CU 14-0200
Other IDs: 4R33MH103231-03
Status last verified: Mar 2024
First submitted: 30 May 2014
Last updated: 2 Apr 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Mittal VA, Gupta T, Orr JM, Pelletier-Baldelli A, Dean DJ, Lunsford-Avery JR, Smith AK, Robustelli BL, Leopold DR, Millman ZB. Physical activity level and medial temporal health in youth at ultra high-risk for psychosis. J Abnorm Psychol. 2013 Nov;122(4):1101-10. doi: 10.1037/a0034085.
PubMed 24364613
Miller TJ, McGlashan TH, Rosen JL, Cadenhead K, Cannon T, Ventura J, McFarlane W, Perkins DO, Pearlson GD, Woods SW. Prodromal assessment with the structured interview for prodromal syndromes and the scale of prodromal symptoms: predictive validity, interrater reliability, and training to reliability. Schizophr Bull. 2003;29(4):703-15. doi: 10.1093/oxfordjournals.schbul.a007040.
PubMed 14989408
Niendam TA, Bearden CE, Zinberg J, Johnson JK, O'Brien M, Cannon TD. The course of neurocognition and social functioning in individuals at ultra high risk for psychosis. Schizophr Bull. 2007 May;33(3):772-81. doi: 10.1093/schbul/sbm020. Epub 2007 Apr 9.
PubMed 17420177
Ragland JD, Ranganath C, Barch DM, Gold JM, Haley B, MacDonald AW 3rd, Silverstein SM, Strauss ME, Yonelinas AP, Carter CS. Relational and Item-Specific Encoding (RISE): task development and psychometric characteristics. Schizophr Bull. 2012 Jan;38(1):114-24. doi: 10.1093/schbul/sbr146. Epub 2011 Nov 28.
PubMed 22124089
Nuechterlein KH, Green MF, Kern RS, Baade LE, Barch DM, Cohen JD, Essock S, Fenton WS, Frese FJ 3rd, Gold JM, Goldberg T, Heaton RK, Keefe RS, Kraemer H, Mesholam-Gately R, Seidman LJ, Stover E, Weinberger DR, Young AS, Zalcman S, Marder SR. The MATRICS Consensus Cognitive Battery, part 1: test selection, reliability, and validity. Am J Psychiatry. 2008 Feb;165(2):203-13. doi: 10.1176/appi.ajp.2007.07010042. Epub 2008 Jan 2.
PubMed 18172019
Patenaude B, Smith SM, Kennedy DN, Jenkinson M. A Bayesian model of shape and appearance for subcortical brain segmentation. Neuroimage. 2011 Jun 1;56(3):907-22. doi: 10.1016/j.neuroimage.2011.02.046. Epub 2011 Feb 23.
PubMed 21352927
Dean DJ, Bryan AD, Newberry R, Gupta T, Carol E, Mittal VA. A Supervised Exercise Intervention for Youth at Risk for Psychosis: An Open-Label Pilot Study. J Clin Psychiatry. 2017 Nov-Dec;78(9):e1167-e1173. doi: 10.4088/JCP.16m11365.
PubMed 29178684

Study at a glance

From the registry record, last updated by the sponsor on 2 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Exercise and Markers of Medial Temporal Health in Youth at Ultra High-risk for Psychosis
ClinicalTrials.gov ID: NCT02155699
Acronym / sponsor ID: CU 14-0200
Conditions: Attenuated Psychosis Syndrome
Keywords: UHR, Remediation, Exercise, Intervention, Psychosis
Study type: Interventional
Recruitment status: Completed
Enrolment: 50 participants (actual)
Lead sponsor: University of Colorado, BoulderUniversity, hospital or other
Collaborators: University of Colorado, Denver, National Institute of Mental Health (NIMH), Northwestern University
Study start: Jul 2014 (actual)
Primary completion: Jul 2022 (actual)
Study completion: Jul 2022 (actual)
First posted: 4 Jun 2014 (estimated)
Results: Posted 13 Mar 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Single group
Masking: Single blind (outcomes assessor)
Number of arms: 3

Arm	Type	Receives
Exercise 1	Experimental	Behavioral: Exercise 165% of V02 Max, 3x per week, 3 months
Exercise 2	Experimental	Behavioral: Exercise 285% of VO2 Max, 2x per week, 3 months
Waitlist	No intervention	–Waitlist (three months)

Who may qualify

Ages: 16 to 24 years
Sex: All
Healthy volunteers: Accepted
Age groups: Child, Adult

Key inclusion criteria (6 listed)

age 16-24
no history of brain injury or neurological disease
no contraindications to exercise training (as assessed by a Clinical Translational Research Center CTRC physician)
no history or current treatment with antipsychotics
no contraindications for being in an magnetic resonance imaging scanner.

Key exclusion criteria (10 listed)

people who are extremely claustrophobic
have a history of significant head injury
other physical disorder that could affect brain functioning
mental retardation
history of substance use disorder within 6 months of screening interview

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Exercise 165% of VO2max and 2 sessions per week	Behavioural	Exercise 1
Exercise 285% intensity and 3 sessions per peek	Behavioural	Exercise 2

Primary outcome

Brain Volume
Time frame: pre-trial, post-trial (3-months)
Medial temporal structures (hippocampus and parahippocampal gyrus) will be delineated automatically using the FMRIB's Integrated Registration and Segmentation Tool algorithm within the FMRIB's Software Library (FSL) image-processing suite. Secondly, the structures will be evaluated with vertex analyses (assessing changes in shape post trial on a per-vertex basis), which will also be carried out utilizing FIRST. Shape/appearance models used in FIRST are constructed from manually segmented images provided by the Center for Morphometric Analysis (CMA, Boston). This approach is different from using a whole-structure summary measure like volume, as it allows visualization of the region of the shape that is changing as well as the type of shape change.

1 secondary outcome

Working Memory Assessment
Time frame: pre-trial, post-trial (3-months)

Results and safety

Results posted to the registry on 13 Mar 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
65% of V02 Max, 3x Per Week, 3 Months - Dosage/Tolerance Study	7	7
85% of VO2 Max, 2x Per Week, 3 Months - Study 1 Dosage	5	2
Waitlist - RCT Study	20	12
High Impact Interval Exercise 80%/95% VO2 Max RCT	18	13

Primary outcome: Brain Volume

Time frame: pre-trial, post-trial (3-months). Mean (Standard Deviation). Unit: Change in mm cubed (baseline -followup)

Measure	Dosage Study Exercise n = 7	Doseage Study Exercise 2 n = 2	RCT High Impact Interval Exercise n = 13	RCT Wait List n = 12
Value	19.8 (50.8)	54.8 (323)	-0.489 (0.104)	-6.28 (1.95)

Population analysed: Withdrew/excluded 3 Dosage (Exercise 2 group); 13 RCT (3 were excluded from the exercise group for not completing all 24 trials, 2 developed substance use disorders after baseline, 1 waitlist converted to a psychosis diagnosis during the protocol and was excluded); Final n=34; Change in hippocampal volume is reported below. On both measures negative scores indicate decreased hippocampal volumes over the study period.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: No exercise intervention related or adjacent events were recorded during the trials period (12 weeks), despite clinical and exercise physiologist assessment. Dose study (moderate intensity) assessed 2x a week for 12 weeks; dose study (high intensity) assessed 3x a week for 12 weeks; RCT assessed 2x a week for 12 weeks; waitlist group assessed at baseline and 3-month follow-up.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Dosage Study: Exercise - Moderate Intensity	0 of 7 (0%)	0 of 7 (0%)	0 of 7
Dosage Study: Exercise High Intensity	0 of 2 (0%)	0 of 2 (0%)	0 of 2
RCT: Exercise - High Impact Interval 95%/80% VO2 Max -32 Week	0 of 13 (0%)	0 of 13 (0%)	0 of 13
RCT: Wait List	0 of 12 (0%)	0 of 12 (0%)	0 of 12

Limitations and caveats (from the sponsor): It is a notable limitation that the current sample size is small; however, the current sample size is comparable or larger than extant randomized control studies in psychosis CHR-p individuals make up a heterogenous population future studies should consider heterogeneity in clinical and cognitive symptoms in larger samples. There are several benefits of exercise not examined by the current study.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 24364613Mittal VA, Gupta T, Orr JM, Pelletier-Baldelli A, Dean DJ, Lunsford-Avery JR, Smith AK, Robustelli BL, Leopold DR, Millman ZB. Physical activity level and medial temporal health in youth at ultra high-risk for psychosis. J Abnorm Psychol. 2013 Nov;122(4):1101-10. doi: 10.1037/a0034085.
Background: PubMed 14989408Miller TJ, McGlashan TH, Rosen JL, Cadenhead K, Cannon T, Ventura J, McFarlane W, Perkins DO, Pearlson GD, Woods SW. Prodromal assessment with the structured interview for prodromal syndromes and the scale of prodromal symptoms: predictive validity, interrater reliability, and training to reliability. Schizophr Bull. 2003;29(4):703-15. doi: 10.1093/oxfordjournals.schbul.a007040.
Background: PubMed 17420177Niendam TA, Bearden CE, Zinberg J, Johnson JK, O'Brien M, Cannon TD. The course of neurocognition and social functioning in individuals at ultra high risk for psychosis. Schizophr Bull. 2007 May;33(3):772-81. doi: 10.1093/schbul/sbm020. Epub 2007 Apr 9.
Background: PubMed 22124089Ragland JD, Ranganath C, Barch DM, Gold JM, Haley B, MacDonald AW 3rd, Silverstein SM, Strauss ME, Yonelinas AP, Carter CS. Relational and Item-Specific Encoding (RISE): task development and psychometric characteristics. Schizophr Bull. 2012 Jan;38(1):114-24. doi: 10.1093/schbul/sbr146. Epub 2011 Nov 28.
Background: PubMed 18172019Nuechterlein KH, Green MF, Kern RS, Baade LE, Barch DM, Cohen JD, Essock S, Fenton WS, Frese FJ 3rd, Gold JM, Goldberg T, Heaton RK, Keefe RS, Kraemer H, Mesholam-Gately R, Seidman LJ, Stover E, Weinberger DR, Young AS, Zalcman S, Marder SR. The MATRICS Consensus Cognitive Battery, part 1: test selection, reliability, and validity. Am J Psychiatry. 2008 Feb;165(2):203-13. doi: 10.1176/appi.ajp.2007.07010042. Epub 2008 Jan 2.
Background: PubMed 21352927Patenaude B, Smith SM, Kennedy DN, Jenkinson M. A Bayesian model of shape and appearance for subcortical brain segmentation. Neuroimage. 2011 Jun 1;56(3):907-22. doi: 10.1016/j.neuroimage.2011.02.046. Epub 2011 Feb 23.
Derived from this study: PubMed 29178684Dean DJ, Bryan AD, Newberry R, Gupta T, Carol E, Mittal VA. A Supervised Exercise Intervention for Youth at Risk for Psychosis: An Open-Label Pilot Study. J Clin Psychiatry. 2017 Nov-Dec;78(9):e1167-e1173. doi: 10.4088/JCP.16m11365.
ADAPT Program Study Site Providing Details for the Clinical TrialLink provided by the sponsor.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Vijay A Mittal, Ph.D. principal investigator

University of Colorado, Boulder

Angela Bryan, Ph.D. principal investigator

University of Colorado, Boulder

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Exercise 1 and Exercise 2 in people with Attenuated Psychosis Syndrome, run by University of Colorado, Boulder at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Brain Volume (time frame: pre-trial, post-trial (3-months)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02155699, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2024.