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Down SyndromeNCT02759887

Relationship Between Down Syndrome (DS) and Alzheimer's Disease (AD)

A study testing biospecimen collection, cognitive assessments and caregiver questionnaire in people with Down Syndrome and Alzheimer's Dementia, run by St. Joseph's Hospital and Medical Center, Phoenix 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

In order to treat individuals with Down syndrome (DS) better and more efficiently and to gain more insights on its relation to Alzheimer's disease (AD), a comprehensive understanding is needed for its progression in the early or preclinical phase using various biomarkers. Read more about this study

Who is it for?
Ages 21 years and olderHealthy volunteers can take part
Conditions the study is for
Down Syndrome, Alzheimer's Dementia
What is being tested?
biospecimen collection, cognitive assessments and caregiver questionnaire
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
1 siteUnited States
Study dates
Nov 2016to Dec 2018
Phase
Interventional
Are there results?
None posted in the registry

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 21 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Subjects with free Trisomy 21.
  • Male or female subjects who are 21 years of age or older.
  • Subjects who are not diagnosed with possible or probable AD or dementia after evaluation NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke- Alzheimer's Disease and Related Disorders Association) criteria.
  • Subjects who live with or have regular visits from a responsible caregiver willing to provide information about the subject's cognitive status.
  • If the subject is incapable of giving informed consent, the caregiver may consent on behalf of the subject (subject must still confirm assent).
  • Subjects with free Trisomy 21.
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  • Male or female subjects who are 40 and older years of age.
  • Subjects who are diagnosed with possible or probable using NINCDS-ADRDA criteria.
  • Subjects who live with or have regular visits from a responsible caregiver willing to provide information about the subject's cognitive status.
  • If the subject is incapable of giving informed consent, the caregiver may consent on behalf of the subject (subject must still confirm assent).
  • Cognitively normal, non-DS individuals.
  • Age-matched to the DS group.
  • Subjects who signed an Institutional Review Board-approved informed consent.

Who cannot join

  • Previous or current diagnosis of a neurodegenerative disorders other than AD or DS, including, but not limited to Parkinson's disease, Pick's disease, fronto-temporal dementia, Huntington's chorea, Creutzfeldt-Jacob disease, normal pressure hydrocephalus, and progressive supranuclear palsy.
  • Previous or current diagnosis of other dementing/neurodegenerative disease (e.g. Parkinson's disease dementia, dementia with Lewy bodies, Lewy body variant AD).
  • Previous or current diagnosis of mixed dementia.
  • Previous or current diagnosis of cognitive impairment resulting from other known etiology.
  • Previous or current diagnosis of clinically significant infarct or possible multi-infarct dementia as defined by the National Institute of Neurological Disorders and Stroke/Association Internationale pour la Recherche et l'Enseignement en Neuroscience (NINDS-AIREN) criteria.
  • Previous or current evidence on screening MRI, computed tomography (CT), or other biomarker studies that suggests an alternate etiology (other than probable AD in patients with AD) for cognitive deficit; or in the case of non-AD controls any evidence on screening MRI, CT, or other biomarker studies that suggests the presence of AD pathology. Brain amyloid-β peptides (Aβ) on Amyloid imaging/PET imaging, however, is expected in many non-AD/DS and all AD/DS subjects, and will not be grounds for exclusion.
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  • Previous or current clinically significant psychiatric disease, as judged by Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria, particularly current major depression or schizophrenia. Patients with dementia who are experiencing behavioral disturbances that may require treatment with psychotropic medications may be entered only after discussion and with the approval of the principal investigator. The investigators should carefully consider whether subjects with behavioral dysfunction will be able to complete the imaging session.
  • Previous or current history of epilepsy or convulsions, except for febrile convulsions during childhood.
  • Current clinically significant hepatic, renal, pulmonary, metabolic, or endocrine disturbances.
  • Current clinically significant cardiovascular disease. Clinically significant cardiovascular disease usually includes one or more of the following: a) cardiac surgery or myocardial infarction within the last 6 months; b) unstable angina; c) coronary artery disease that required an increase in medication within the last 3 months; d) decompensated congestive heart failure; e) significant cardiac arrhythmia or conduction disturbance, particularly those resulting in a trial or ventricular fibrillation, or causing syncope, near syncope, or other alterations in mental status; f) severe mitral or aortic valvular disease; g) uncontrolled high blood pressure; h) congenital heart disease) .
  • Current history of drug or alcohol abuse within the last year, or prior prolonged history of abuse.
  • Current clinically significant infectious disease, including known Acquired Immune Deficiency Syndrome (AIDS) or Human Immunodeficiency Virus (HIV) infection or previous positive test for hepatitis.
  • Women of childbearing potential who are not surgically sterile, not refraining from sexual activity, or not using reliable methods of contraception. Women of childbearing potential must not be pregnant (negative serum beta-hCG [human chorionic gonadotropin] at the time of screening and negative urine beta-hCG on the day of imaging) or lactating at screening. Women must avoid becoming pregnant, and must agree to refrain from sexual activity or to use reliable contraceptive methods for 30 days prior to and 30 days after administration of radiopharmaceutical imaging agents in this study. In order to participate in this study, sexually active females must be either: two or more years post-menopausal or surgically sterilized, or must be using an acceptable form of contraception (oral contraceptives for at least three months or an IUD (intrauterine device) for at least two months prior to the start of the screening visit, or various barrier methods, e.g., diaphragm or combination condom and spermicide).
  • Subjects who, in the opinion of the research team, are otherwise unsuitable for a study of this type.
  • Subjects who have a history of relevant severe drug allergy or hypersensitivity.
  • Subjects who have received an investigational medication within the last 30 days. Additionally, the time between the last dose of the previous experimental medication and enrollment (completion of screening assessments) must be at least equal to 5 times the terminal half-life of the previous experimental medication.
  • Subjects who have ever participated in an experimental study with an amyloid targeting therapy (e.g., immunotherapy, secretase inhibitor) may not be enrolled unless it can be demonstrated that the subject received only placebo in the course of the trial.
  • Current clinically significant medical comorbidities, as indicated by history, physical exam, or laboratory evaluations, that might pose a potential safety risk, interfere with the absorption or metabolism of the study medication, or limit interpretation of the trial results. These include but are not limited to clinically significant hepatic, renal, pulmonary, metabolic or endocrine disease, and cancer.
  • Subjects who have received a radiopharmaceutical for imaging or therapy within the past 7 days prior to the imaging session for this study.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • St. Joseph's Hospital and Medical Center

    Phoenix, Arizona, 85013

Other trials in United States

About this study

Official title: Longitudinal Assessment of Amyloid Positron Emission Tomography (PET), Fludeoxyglucose F18 (FDG) PET, Tau PET, Magnetic Resonance Imaging (MRI), and Blood Spot Ribonucleic Acid (RNA) in Down Syndrome Individuals With and Without Alzheimer's Dementia and Normal Controls

In order to treat individuals with Down syndrome (DS) better and more efficiently and to gain more insights on its relation to Alzheimer's disease (AD), a comprehensive understanding is needed for its progression in the early or preclinical phase using various biomarkers. DS is a significant risk factor for the early development of AD, with plaques and tangles typically developing by age 35. A better understanding is needed of early markers of the disease in DS patients. Additionally the DS population represents a unique group - due to this elevated risk for AD - to examine biomarkers that may translate in general outside of the DS population to individuals at risk for developing late onset AD. In this proposal, the researchers will assess the longitudinal changes of various biomarkers in a cohort of individuals similar in design to the cross-sectional sectional study in the preliminary data.

Read the detailed description

This study will recruit from three experimental groups: (1)The DS (adult) group will consist of 15 DS subjects aged 21 and older who do not qualify for the diagnosis of dementia at the beginning of the study. (2)The DS/AD group will consist of 15 DS subjects aged 40 and older who do qualify for the diagnosis of dementia by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria. Diagnoses will be by standard consensus review of all cases. (3)Normal control (NC) adult will consist of 10 cognitively normal, non-DS individuals, age-matched to the DS group. Blood will be collected to assess apolipoprotein E (ApoE) genotype. Participation in the dried blood spot collection (DBSC) will be an optional sub-study. Only participants and/or their caregivers/legally authorized representatives indicating they wish to have DBSC performed on the consent will provide specimens.

Being tested
biospecimen collection, cognitive assessments, caregiver questionnaire, Florbetapir F18 imaging, MRI
Medical subject headings
Down Syndrome, Alzheimer Disease

What participants receive

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

  • biospecimen collectionProcedure or surgery

    Blood: ApoE genotyping, comprehensive metabolic panel, RNA sequencing. Urine: beta-hCG (human corionic gonadotropin) testing.

  • cognitive assessmentsOther

    Dementia Questionnaire for People with Learning Disabilities; Mini-Mental State Examination; Severe Impairment Battery; Vineland Adaptive Behavior Scale; Arizona Memory Assessment for Intellectual Disability; Kaufman Brief Intelligence Test; Nepsy Mazes; and, Timed Up and Go.

  • caregiver questionnaireOther

  • Florbetapir F18 imagingProcedure or surgery

    Used in small doses to image brain amyloid-beta deposits in human beings. Radioactivity necessary to create the positron emission tomography (PET) images. Radiation exposure is slightly more than a person would receive from a routine clinical head computed tomography scan.

  • MRIProcedure or surgery

    Magnetic resonance imaging of the head and brain.

  • Fludeoxyglucose F18 (FDG)Procedure or surgery

    Injected intravenously during a PET scan and is a marker for the tissue uptake of glucose; a radiopharmaceutical compound.

  • Tau PetProcedure or surgery

    Also called F-AV-1451

    Administered during a PET, in small amounts, necessary to create the scan images. Radioactive. The total amount of radiation is about the same that a patient receives from a routine abdominal/pelvis computerized tomography.

  • ActigraphyProcedure or surgery

    Also called actimetry

    A non-invasive method of monitoring human rest and activity cycles. A small actigraph unit is worn to measure gross motor activity. The unit is usually worn on the wrist.

Study groups in NCT02759887
Study groupRoleWhat they receive
DS adult groupOtherConsists of 15 DS subjects aged 21 and older who do not qualify for the diagnosis of dementia at the beginning of the study. Interventions include biospecimen collection, cognitive assessments, caregiver questionnaire, Florbetapir F18 imaging, MRI, Fludeoxyglucose F18 (FDG), Tau Pet, Actigraphy.
Receives: Procedure: biospecimen collection; Other: cognitive assessments; Other: caregiver questionnaire; Procedure: Florbetapir F18 imaging; Procedure: MRI; Procedure: Fludeoxyglucose F18 (FDG); Procedure: Tau Pet; Procedure: Actigraphy
DS/AD groupOtherConsists of 15 DS subjects aged 40 and older who do qualify for the diagnosis of dementia by DSM-IV criteria. Diagnoses will be by standard consensus review of all cases. Interventions include biospecimen collection, cognitive assessments, caregiver questionnaire, Florbetapir F18 imaging, MRI, Fludeoxyglucose F18 (FDG), Tau Pet, Actigraphy.
Receives: Procedure: biospecimen collection; Other: cognitive assessments; Other: caregiver questionnaire; Procedure: Florbetapir F18 imaging; Procedure: MRI; Procedure: Fludeoxyglucose F18 (FDG); Procedure: Tau Pet; Procedure: Actigraphy
NC adultOtherConsists of 10 cognitively normal, non-DS individuals, age-matched to the DS adult group. Interventions include biospecimen collection, cognitive assessments, Florbetapir F18 imaging, MRI, Fludeoxyglucose F18 (FDG), Tau Pet, Actigraphy.
Receives: Procedure: biospecimen collection; Other: cognitive assessments; Procedure: Florbetapir F18 imaging; Procedure: MRI; Procedure: Fludeoxyglucose F18 (FDG); Procedure: Tau Pet; Procedure: Actigraphy

What is being measured

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

  1. Florbetapir PET - change between timeframes

    The researchers will use multi-modal partial least squares (MMPLS) to integrate the volumetric MRI, tau PET, FDG PET and florbetapir PET data and investigate the potential for increased sensitivity to examine the longitudinal changes related to both brain structure and fibrillar amyloid depositions. The MMPLS based subject scores, which is free from multiple comparisons, will be the primary measure integrating information from imaging modalities. The combined primary measures will be used each to compute the number of DS or DS/AD patients in the treatment and in the placebo arms needed for a 60 month clinical trial with 80% power, two-tailed p=0.05 and assumed treatment effects of 25%. These estimated samples are indicative of each biomarker for their sensitivity.

    Measured: Year 1, Year 2-3

  2. tau PET - change between timeframes

    The researchers will use multi-modal partial least squares (MMPLS) to integrate the volumetric MRI, tau PET, FDG PET and florbetapir PET data and investigate the potential for increased sensitivity to examine the longitudinal changes related to both brain structure and fibrillar amyloid depositions. The MMPLS based subject scores, which is free from multiple comparisons, will be the primary measure integrating information from imaging modalities. The combined primary measures will be used each to compute the number of DS or DS/AD patients in the treatment and in the placebo arms needed for a 60 month clinical trial with 80% power, two-tailed p=0.05 and assumed treatment effects of 25%. These estimated samples are indicative of each biomarker for their sensitivity.

    Measured: Year 1, Year 2-3

  3. FDG PET - change between timeframes

    The researchers will use multi-modal partial least squares (MMPLS) to integrate the volumetric MRI, tau PET, FDG PET and florbetapir PET data and investigate the potential for increased sensitivity to examine the longitudinal changes related to both brain structure and fibrillar amyloid depositions. The MMPLS based subject scores, which is free from multiple comparisons, will be the primary measure integrating information from imaging modalities. The combined primary measures will be used each to compute the number of DS or DS/AD patients in the treatment and in the placebo arms needed for a 60 month clinical trial with 80% power, two-tailed p=0.05 and assumed treatment effects of 25%. These estimated samples are indicative of each biomarker for their sensitivity.

    Measured: Year 1, Year 2-3

  4. MRI - change between timeframes

    The researchers will use multi-modal partial least squares (MMPLS) to integrate the volumetric MRI, tau PET, FDG PET and florbetapir PET data and investigate the potential for increased sensitivity to examine the longitudinal changes related to both brain structure and fibrillar amyloid depositions. The MMPLS based subject scores, which is free from multiple comparisons, will be the primary measure integrating information from imaging modalities. The combined primary measures will be used each to compute the number of DS or DS/AD patients in the treatment and in the placebo arms needed for a 60 month clinical trial with 80% power, two-tailed p=0.05 and assumed treatment effects of 25%. These estimated samples are indicative of each biomarker for their sensitivity.

    Measured: Year 1, Year 2-3

Secondary outcomes (1)

  1. dried blood spot collection (DBSC) analysis - change between timeframes

    (a) Detect and track RNA biomarkers longitudinally from a single dried blood spot (DBS) using next generation RNA sequencing (RNA-Seq) in prospectively assessed DS, DS/AD and NC, (b) Study and identify biomarkers with the greatest rate of change in DS patients who are at differential risk levels for the development of AD dementia, and (c) Correlate the RNA biomarkers with imaging (FDG-PET, FBP (Florbetapir F18)-PET, MRI, tau PET) that are concurrently being gathered in the proposed study populations.

    Measured: Year 1, Year 2-3

Timeline

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

  1. First posted3 May 2016 (estimated)
  2. Study startNov 2016
  3. Primary completionDec 2018
  4. Study completionDec 2018

Resources

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
Diagnosis
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02759887
Sponsor's protocol ID
PHX-16-0028-70-03
Status last verified
Oct 2019
First submitted
15 Apr 2016
Last updated
29 Oct 2019
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A study testing biospecimen collection, cognitive assessments and caregiver questionnaire in people with Down Syndrome and Alzheimer's Dementia, run by St. Joseph's Hospital and Medical Center, Phoenix 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 13 inclusion and 19 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 29 Oct 2019. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Florbetapir PET - change between timeframes (time frame: Year 1, Year 2-3). The study lists 4 primary outcomes in all. 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 NCT02759887.

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 29 Oct 2019.

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