Mild Cognitive ImpairmentPhase 2NCT01463384

Minocycline in Patients With Alzheimer's Disease

A Phase 2 study testing Minocycline in people with Mild Cognitive Impairment and Alzheimer's Disease, run by Huntington Medical Research Institutes 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 55 to 90 yearsHealthy volunteers can take part
Conditions the study is for: Mild Cognitive Impairment, Alzheimer's Disease
What is being tested?: Minocycline
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 13 participants
Where: 1 siteUnited States
Study dates: Sep 2011to Oct 2012
Phase: Phase 2
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 55 to 90 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Cognitively normal elderly subjects between the ages of 55-90 and patients aged 55 - 90 years who have mild cognitive impairment (MCI) or clinically defined Alzheimer's disease.

Who cannot join

Any person with medical devices such as cardiac pacemakers/defibrillators or neuro-implants as they are contra-indications for MRI/MRS exam.
Since the effects of MRI are unknown to the fetus or unborn child, any person who is or may be pregnant will be excluded from the study.
History of known allergy or intolerance to minocycline or any other tetracycline
Impaired renal function (plasma Creatinine) or blood urea nitrogen (BUN) levels exceeds twice normal upper limit which can result in higher serum levels of tetracycline, azotemia, hyperphosphatemia and acidosis.

Trial locations and contacts

1 site in 1 country.

United States1 site

Huntington Medical Research Institutes
Pasadena, California, 91105

Other trials in United States

About this study

Official title: MRI and MRS Diagnosis and Treatment Monitoring of Alzheimer's Disease With Novel Therapy

Cognitively normal individuals, patients with Mild Cognitive Impairment (MCI) or Alzheimer's Disease (AD) will undergo clinical screening, neuropsychological tests, blood and urine analyses, quantitative magnetic resonance imaging (MRI) and proton (1H ) and carbon 13 (13C) magnetic resonance spectroscopy (MRS). Each individual will receive minocycline oral administration for 4 weeks initially, after which MRI, MRS and neuropsychological results will be recorded. If no adverse side effects occur, subjects will continue minocycline administration for an additional 5 months.

Read the detailed description

In the course of on-going trials of novel MRI procedures for Neurological Diagnosis, the investigators have established non-invasive BIOMARKERS (Note: Biomarkers are objective Laboratory tests used in, but not replacing Clinical diagnostic criteria of any disease,in this case age-related dementia of the Alzheimer type and its pre-clinical forms including Mild Cognitive Impairment - MCI) which significantly assist in the Diagnosis of Alzheimer's Disease. MRS, rather like blood tests which are applied for screening and exclusion of medical disorders, provides a pattern of brain chemicals from which this and many other diagnoses have become available (see: Magnetic Resonance Spectroscopy in Neurological Diagnosis: E.R Danielsen and B.D. Ross, Marcel Dekker New York, 1999). Diagnosis of Alzheimer's Disease has hitherto been exclusively a clinical diagnosis, made on the basis of non-specific tests by the treating physician/neurologist. Furthermore, treatments have been of limited efficacy so that the pressure for conclusive diagnosis or an objective characterization of disease progression (or better, regression) has not been a priority. This conservative approach to Alzheimer's Disease changed in 2010 with the Report of National Institutes of Aging. First: The failures of treatment have been ascribed to introduction only in patients with advanced disease ("dementia"). Second: A preliminary form of AD, known as pre-clinical or Mild Cognitive Impairment, has been recognized, distinct from, and generally earlier in the disease course. Third: A new set of diagnostic criteria, which include objective 'biomarkers', from cerebrospinal fluid, genetic and imaging analyzes, has been accepted by the Expert Panel. Finally, Clinical trials of existing and new drugs for Alzheimer's Disease are expected to yield better results if initiated earlier - in the pre-clinical phase - and the outcomes evaluated by the earlier changes in an approved panel of biomarkers.

Conditions: Mild Cognitive Impairment, Alzheimer's Disease
Being tested: Minocycline
Keywords: Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Neuroinflammation, Mild Cognitive Impairment, Alzheimer's Disease, Minocycline
Medical subject headings: Cognitive Dysfunction, Alzheimer Disease, Neuroinflammatory Diseases, cyclopia sequence

What participants receive

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

MinocyclineDrug
Also called Tetracycline
50mg, twice daily for 6 months.

Study groups in NCT01463384
Study group	Role	What they receive
Minocycline	Active comparator	Subjects will be administered 50mg minocycline twice daily. Receives: Drug: Minocycline

What is being measured

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

Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
RBANS is a brief neurocognitive battery with four alternate forms, measuring immediate and delayed memory, attention, language, and visuospatial skills. RBANS was developed as a stand-alone "core" battery for the detection and neurocognitive characterization of dementia and as a brief neurocognitive battery for the detection and tracking of neurocognitive deficits in a variety of disorders. (Reference: http://rbans.com/)
Qualitative Description of Index Scores:
Index Score Classification 130 and above Very Superior 120-129 Superior 110-119 High Average 90-109 Average 80-89 Low Average 70-79 Borderline 69 and below Extremely Low
Psychometric range for RBANS:
AD 0 - 77 MCI 78 - 99 Normal > 100
Range of scores: Minimum = 0, Maximum = 130
Values are reported below for Baseline, averaged for 1-3 months, and averaged for 4-6 months during minocycline administration.
Measured: Baseline values, 1-3 Months Values (averaged), 4-6 Months Values (averaged)
Hippocampal Volumes Measured in Three Groups: Alzheimer Disease (AD), Mild Cognitive Impairment (MCI) and Normal, Age-matched Controls (NC).
Using magnetic resonance images acquired, hippocampal volume was measured monthly for 6 months.
Normal range for hippocampal volume in aged-matched controls is 6.6 - 8.8 cm^3.
Values are reported below for Baseline, averaged for 1-3 months, and averaged for 4-6 months during minocycline administration.
Measured: Baseline values, 1-3 Months Values (averaged), 4-6 Months Values (averaged)
Biomarker NAA/mI Measured in Three Groups: Alzheimer Disease (AD), Mild Cognitive Impairment (MCI) and Normal, Age-matched Controls (NC)
It has been demonstrated in numerous studies over the past decade that magnetic resonance spectroscopy (MRS) can be used for the diagnosis of Alzheimer's disease. By measuring an area within the posterior cingulate gyrus, one can obtain a biochemical signature of that region in AD whereby NAA is reduced and mI is increased.
These two biomarkers, N-acetylaspartate (NAA, a neuronal marker) and myo-inositol (mI, a glial marker) were quantified and then used to calculate NAA/mI (an index currently widely used for AD and MCI diagnosis).
Scale of MRS biomarkers for aged-matched controls: NAA = 1.43, mI = 0.60, NAA/mI = 2.38. Any value lower than NAA/mI of 2.38 are considered not normal.
Values are reported below for Baseline, averaged for 1-3 months, and averaged for 4-6 months during minocycline administration.
Measured: Baseline values, 1-3 Months Values (averaged), 4-6 Months Values (averaged)

Timeline

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

Sep 2011Oct 2012

First posted1 Nov 2011 (estimated)
Study startSep 2011
Primary completionOct 2012
Study completionOct 2012

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.
Other trials for Mild Cognitive ImpairmentStudies 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 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 13 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01463384
Sponsor's protocol ID: LKW-AB34
Status last verified: Sep 2014
First submitted: 25 Oct 2011
Last updated: 25 Sep 2014
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Mild Cognitive Impairment trials

Study at a glance

From the registry record, last updated by the sponsor on 25 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: MRI and MRS Diagnosis and Treatment Monitoring of Alzheimer's Disease With Novel Therapy
ClinicalTrials.gov ID: NCT01463384
Acronym / sponsor ID: LKW-AB34
Conditions: Mild Cognitive Impairment, Alzheimer's Disease
Keywords: Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Neuroinflammation, Mild Cognitive Impairment, Alzheimer's Disease, Minocycline
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 13 participants (actual)
Lead sponsor: Huntington Medical Research InstitutesUniversity, hospital or other
Study start: Sep 2011
Primary completion: Oct 2012 (actual)
Study completion: Oct 2012 (actual)
First posted: 1 Nov 2011 (estimated)
Results: Posted 25 Sep 2014

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: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Minocycline	Active comparator	Drug: MinocyclineSubjects will be administered 50mg minocycline twice daily.

Who may qualify

Ages: 55 to 90 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (1 listed)

Cognitively normal elderly subjects between the ages of 55-90 and patients aged 55 - 90 years who have mild cognitive impairment (MCI) or clinically defined Alzheimer's disease.

Key exclusion criteria (4 listed)

Any person with medical devices such as cardiac pacemakers/defibrillators or neuro-implants as they are contra-indications for MRI/MRS exam.
Since the effects of MRI are unknown to the fetus or unborn child, any person who is or may be pregnant will be excluded from the study.
History of known allergy or intolerance to minocycline or any other tetracycline
Impaired renal function (plasma Creatinine) or blood urea nitrogen (BUN) levels exceeds twice normal upper limit which can result in higher serum levels of tetracycline, azotemia, hyperphosphatemia and acidosis.

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
MinocyclineAlso: Tetracycline50mg, twice daily for 6 months.	Drug	Minocycline

Primary outcome

Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
Time frame: Baseline values, 1-3 Months Values (averaged), 4-6 Months Values (averaged)
RBANS is a brief neurocognitive battery with four alternate forms, measuring immediate and delayed memory, attention, language, and visuospatial skills. RBANS was developed as a stand-alone "core" battery for the detection and neurocognitive characterization of dementia and as a brief neurocognitive battery for the detection and tracking of neurocognitive deficits in a variety of disorders. (Reference: http://rbans.com/) Qualitative Description of Index Scores: Index Score Classification 130 and above Very Superior 120-129 Superior 110-119 High Average 90-109 Average 80-89 Low Average 70-79 Borderline 69 and below Extremely Low Psychometric range for RBANS: AD 0 - 77 MCI 78 - 99 Normal > 100 Range of scores: Minimum = 0, Maximum = 130 Values are reported below for Baseline, averaged for 1-3 months, and averaged for 4-6 months during minocycline administration.
Hippocampal Volumes Measured in Three Groups: Alzheimer Disease (AD), Mild Cognitive Impairment (MCI) and Normal, Age-matched Controls (NC).
Time frame: Baseline values, 1-3 Months Values (averaged), 4-6 Months Values (averaged)
Using magnetic resonance images acquired, hippocampal volume was measured monthly for 6 months. Normal range for hippocampal volume in aged-matched controls is 6.6 - 8.8 cm^3. Values are reported below for Baseline, averaged for 1-3 months, and averaged for 4-6 months during minocycline administration.
Biomarker NAA/mI Measured in Three Groups: Alzheimer Disease (AD), Mild Cognitive Impairment (MCI) and Normal, Age-matched Controls (NC)
Time frame: Baseline values, 1-3 Months Values (averaged), 4-6 Months Values (averaged)
It has been demonstrated in numerous studies over the past decade that magnetic resonance spectroscopy (MRS) can be used for the diagnosis of Alzheimer's disease. By measuring an area within the posterior cingulate gyrus, one can obtain a biochemical signature of that region in AD whereby NAA is reduced and mI is increased. These two biomarkers, N-acetylaspartate (NAA, a neuronal marker) and myo-inositol (mI, a glial marker) were quantified and then used to calculate NAA/mI (an index currently widely used for AD and MCI diagnosis). Scale of MRS biomarkers for aged-matched controls: NAA = 1.43, mI = 0.60, NAA/mI = 2.38. Any value lower than NAA/mI of 2.38 are considered not normal. Values are reported below for Baseline, averaged for 1-3 months, and averaged for 4-6 months during minocycline administration.

Results and safety

Results posted to the registry on 25 Sep 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Minocycline	13	13

Primary outcome: Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)

Time frame: Baseline values, 1-3 Months Values (averaged), 4-6 Months Values (averaged). Mean (Standard Deviation). Unit: units on a scale

Measure	Minocycline AD n = 4	Minocycline MCI n = 1	Minocycline NC n = 8
Baseline Values	49 (8)	81	106 (13)
Averaged Values for Months 1-3	32.5 (3.4)	58.7	108.4 (26)
Averaged Values for Months 4-6	32.9 (4.2)	63.8	123.6 (37.1)

Primary outcome: Hippocampal Volumes Measured in Three Groups: Alzheimer Disease (AD), Mild Cognitive Impairment (MCI) and Normal, Age-matched Controls (NC).

Time frame: Baseline values, 1-3 Months Values (averaged), 4-6 Months Values (averaged). Mean (Standard Deviation). Unit: cm^3

Measure	Minocycline AD n = 4	Minocycline MCI n = 1	Minocycline NC n = 8
Baseline Values	5.49 (1.14)	6.35	6.98 (1.18)
Averaged Values for Months 1-3	5.42 (1.06)	6.30	6.92 (0.48)
Averaged Values for Months 4-6	4.94 (1.2)	7.60	6.82 (0.45)

Primary outcome: Biomarker NAA/mI Measured in Three Groups: Alzheimer Disease (AD), Mild Cognitive Impairment (MCI) and Normal, Age-matched Controls (NC)

Time frame: Baseline values, 1-3 Months Values (averaged), 4-6 Months Values (averaged). Mean (Standard Deviation). Unit: Ratio

Measure	Minocycline AD n = 4	Minocycline MCI n = 1	Minocycline NC n = 8
Baseline Values	1.69 (0.38)	1.87	2.42 (0.08)
Averaged Values for Months 1-3	1.78 (0.61)	1.80	2.44 (0.26)
Averaged Values for Months 4-6	1.84 (0.61)	2.08	2.47 (0.41)

Adverse events

Time frame: 7 months. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Minocycline	0 of 13 (0%)	0 of 13 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related InfoLink provided by the sponsor.

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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.

Brian D Ross principal investigator

Huntington Medical Research Institutes

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

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Minocycline in people with Mild Cognitive Impairment and Alzheimer's Disease, run by Huntington Medical Research Institutes 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 1 inclusion and 4 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 25 Sep 2014. 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.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Sep 2014). 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?

Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) (time frame: Baseline values, 1-3 Months Values (averaged), 4-6 Months Values (averaged)). The study lists 3 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 NCT01463384.

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 25 Sep 2014.