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Bipolar DepressionPhase 2ALIGNNCT02155972

The Safety and Effectiveness of Probiotic Supplementation on Bipolar Depression

A Phase 2 study testing Bifidobacterium infantis in people with Bipolar Depression, run by Women's College Hospital at 1 site in Canada.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is an 8-week randomized, double-blind placebo-controlled proof of concept study assessing the combination of a mood stabilizer + Align in the treatment of participants with a bipolar depressive episode. The study has two treatment arms: mood stabilizer plus placebo and mood stabilizer plus Align. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Bipolar Depression
What is being tested?
Bifidobacterium infantis
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
16 participants
Where
1 siteCanada
Study dates
May 2013to 31 Jul 2018
Phase
Phase 2
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 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Informed of the nature of the study and have agreed to and are able to read, review, and sign the informed consent form. The informed consent document will be written in English, therefore the volunteer must have the ability to read and communicate in English
  • Male and Female participants 18 - 65 years of age ,inclusive, at the time of screening
  • Demonstrates a diagnosis of bipolar depression (type I or II) according to the Mini International Neuropsychiatric interview (MINI)
  • Is not hospitalized or institutionalized (outpatient) at the time of screening
  • Have been on a stable (unchanged) and adequate dose of one of the permissible medications for at least 8 weeks prior to screening (lithium, valproate/divalproex, carbamazepine, lamotrigine, quetiapine/quetiapine XR, olanzapine, or risperidone)
  • Demonstrates a maximum HAM-D score of 24 at screening and baseline visits
  • Female participants Must:
  • Not be breast feeding Not be pregnant or seeking to get pregnant during the course of this study. Be menopausal or using an acceptable method of birth control (implants, injectables, combined oral contraceptives, IUDs, sexual abstinence or a vasectomized partner)

Who cannot join

  • Demonstrates or reports a history of any of the DSM-IV criteria for classification of substance abuse/dependence disorders in the past year.
  • Demonstrates the presence of active eating disorders, schizophrenia or schizoaffective disorder
  • Demonstrates current psychotic symptoms
  • Demonstrates a Young Mania Rating Scale (YMRS) score of >12 at screening
  • Demonstrates active suicidality based on the C-SSR scale
  • Reports using any potent cytochrome P450 inhibitors (such as chloramphenicol, antifungal agents) during the 14 days prior to screening
Show all 14Show fewer
  • Reports a history of electroconvulsive therapy (ECT) during the 90 days prior to screening
  • Reports using Align or any other probiotic supplement within the last year prior to screening
  • Reports a history of allergic response(s) to components of Align (such as Bifidobacterioum), or any other related drug.
  • Reports a presence or history of any medical conditions that would affect drug pharmacokinetics (gastrointestinal conditions such as chroris or colitus).
  • Reports a history of any immunocompromising condition (such as HIV, lymphoma, patients undergoing long-term corticosteroid treatment)
  • Currently experiencing nausea, fever, vomiting, bloody diarrhea or severe abdominal pain
  • Reports use of other natural health products (in addition to probiotics) that affect depression (such as St. Johns Wart, Tryptophan) within the last 6 months prior to screening
  • Reports frequent consumption of foods rich in / enriched with probiotics (e.g. yoghurt, drinks, e.t.c).

Trial locations and contacts

1 site in 1 country.

Canada1 site

  • Women's college Research Institute

    Toronto, Ontario, M5G1N8

Other trials in Canada

About this study

Official title: The Safety and Effectiveness of Probiotic Supplementation on Bipolar Depression: a Proof of Concept Randomized Controlled Trial

This is an 8-week randomized, double-blind placebo-controlled proof of concept study assessing the combination of a mood stabilizer + Align in the treatment of participants with a bipolar depressive episode. The study has two treatment arms: mood stabilizer plus placebo and mood stabilizer plus Align.

The dose of mood stabilizer will be in accordance with clinical practice guidelines and the dose for Align will be 1 capsule per day as per appropriate product dosing.

Read the detailed description

Depression has emerged as the major challenge for short- and long-term management of bipolar disorder; new treatments are needed to help control this illness. Studies indicate that probiotics in the stomach improves mood and reduces anxiety symptoms lending further support to the notion that probiotic bacteria positively influence emotional states. We propose to evaluate the effectiveness of the combination of mood stabilizer and Align, a probiotic as compared to mood stabilizer monotherapy.

The primary goal of this feasibility study is to determine the safety and tolerability of Align as an add on to accepted monotherapy treatment in BD. Secondary Objective:1)To evaluate the effectiveness of the combination of mood stabilizer + Align compared to mood stabilizer monotherapy in treatment of BD. 2) to determine if Align +mood stabilizer combination will reduce anxiety symptoms.

An 8-week randomized, double-blind placebo-controlled proof of concept study assessing the combination a mood stabilizer + Align in the treatment of patients with an bipolar depressive episode. The study has two treatment arms: mood stabilizer + placebo and mood stabilizer + Align. Participants will be assessed \& administered study scales at screening, baseline \& weeks 2,4,6 and 8. the dose for mood stabilizer will be in accordance with clinical practice guidelines and Align - 1 capsule/day.

Being tested
Bifidobacterium infantis, Placebo
Keywords
Bipolar, Depression, Probiotic, ALIGN, HAMD, STAI, YMRS, CGI, SDS, WHOQOL-BREF, C-SSRS, TSES
Medical subject headings
Bipolar Disorder, Depression

What participants receive

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

  • Bifidobacterium infantisDietary supplement

    Also called ALIGN

    Probiotic supplement

  • PlaceboOther

    Placebo capsules

Study groups in NCT02155972
Study groupRoleWhat they receive
Bifidobacterium infantisActive comparatorBifidobacterium infantis (Align) 10.00 million cfu capsule once daily
Receives: Dietary Supplement: Bifidobacterium infantis
PlaceboPlacebo comparatorPlacebo capsule once daily
Receives: Other: Placebo

What is being measured

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

  1. safety and tolerability of Align

    Tolerability will be assessed using the Toronto Side Effect Scale (TSES). It is a 32-item instrument that is designed to establish incidence, frequency, and severity of central nervous system (CNS), gastrointestinal (GI), and sexual side effects. We will also assess the proportion of participants withdrawing from study due to inadequate control of depressive symptoms or treatment emergent mania

    Measured: 8 weeks

Secondary outcomes (2)

  1. The effectiveness of the combination of mood stabilizer + Align

    This will be assessed through the change in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline to the final visit (week 8)

    Measured: 8 weeks

  2. evaluate the combination of mood stabilizer + Align as compared to mood stabilizer monotherapy for participants with bipolar depression with respect to anxiety symptoms and global function/overall improvement

    Anxiety symptoms will be assessed by looking at the mean change in the State and Trait Anxiety Index (STAI) total score, quality of life will be assessed with the World Health Organization Quality of Life (WHO-QOL) scale and global functioning will be accessed via mean change in the following: Sheehan Disability Scale (SDS) score, the clinical global impressions (CGI) severity of illness score, the CGI-Improvement scale and the CGI Participant Assessment. All measures will be evaluated looking at change from baseline to week 8

    Measured: 8 weeks

Timeline

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

  1. First posted4 Jun 2014 (estimated)
  2. Study startMay 2013
  3. Primary completion31 Jul 2018
  4. Study completion31 Jul 2018

Why it stopped: The trial was terminated because of inability to recruit the needed number of participants

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Participants are randomized to receive either ALIGN (probiotic) or Placebo
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02155972
Sponsor's protocol ID
179489
Acronym
ALIGN
Status last verified
Nov 2018
First submitted
28 May 2014
Last updated
8 Nov 2018
Results posted
No
Data monitoring committee
No

Publications

  • Bercik P, Verdu EF, Foster JA, Macri J, Potter M, Huang X, Malinowski P, Jackson W, Blennerhassett P, Neufeld KA, Lu J, Khan WI, Corthesy-Theulaz I, Cherbut C, Bergonzelli GE, Collins SM. Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry in mice. Gastroenterology. 2010 Dec;139(6):2102-2112.e1. doi: 10.1053/j.gastro.2010.06.063. Epub 2010 Jun 27.

    PubMed 20600016

  • Cryan JF, O'Mahony SM. The microbiome-gut-brain axis: from bowel to behavior. Neurogastroenterol Motil. 2011 Mar;23(3):187-92. doi: 10.1111/j.1365-2982.2010.01664.x.

    PubMed 21303428

  • Forsythe P, Sudo N, Dinan T, Taylor VH, Bienenstock J. Mood and gut feelings. Brain Behav Immun. 2010 Jan;24(1):9-16. doi: 10.1016/j.bbi.2009.05.058. Epub 2009 May 28.

    PubMed 19481599

  • Rhee SH, Pothoulakis C, Mayer EA. Principles and clinical implications of the brain-gut-enteric microbiota axis. Nat Rev Gastroenterol Hepatol. 2009 May;6(5):306-14. doi: 10.1038/nrgastro.2009.35.

    PubMed 19404271

  • Sudo N, Chida Y, Aiba Y, Sonoda J, Oyama N, Yu XN, Kubo C, Koga Y. Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J Physiol. 2004 Jul 1;558(Pt 1):263-75. doi: 10.1113/jphysiol.2004.063388. Epub 2004 May 7.

    PubMed 15133062

  • Neufeld KM, Kang N, Bienenstock J, Foster JA. Reduced anxiety-like behavior and central neurochemical change in germ-free mice. Neurogastroenterol Motil. 2011 Mar;23(3):255-64, e119. doi: 10.1111/j.1365-2982.2010.01620.x. Epub 2010 Nov 5.

    PubMed 21054680

  • Diaz Heijtz R, Wang S, Anuar F, Qian Y, Bjorkholm B, Samuelsson A, Hibberd ML, Forssberg H, Pettersson S. Normal gut microbiota modulates brain development and behavior. Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):3047-52. doi: 10.1073/pnas.1010529108. Epub 2011 Jan 31.

    PubMed 21282636

  • Lyte M, Li W, Opitz N, Gaykema RP, Goehler LE. Induction of anxiety-like behavior in mice during the initial stages of infection with the agent of murine colonic hyperplasia Citrobacter rodentium. Physiol Behav. 2006 Oct 30;89(3):350-7. doi: 10.1016/j.physbeh.2006.06.019. Epub 2006 Aug 2.

    PubMed 16887154

  • Goehler LE, Gaykema RP, Opitz N, Reddaway R, Badr N, Lyte M. Activation in vagal afferents and central autonomic pathways: early responses to intestinal infection with Campylobacter jejuni. Brain Behav Immun. 2005 Jul;19(4):334-44. doi: 10.1016/j.bbi.2004.09.002.

    PubMed 15944073

  • Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM, Dinan TG, Bienenstock J, Cryan JF. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):16050-5. doi: 10.1073/pnas.1102999108. Epub 2011 Aug 29.

    PubMed 21876150

  • Judd LL, Akiskal HS, Schettler PJ, Endicott J, Maser J, Solomon DA, Leon AC, Rice JA, Keller MB. The long-term natural history of the weekly symptomatic status of bipolar I disorder. Arch Gen Psychiatry. 2002 Jun;59(6):530-7. doi: 10.1001/archpsyc.59.6.530.

    PubMed 12044195

  • Judd LL, Akiskal HS, Schettler PJ, Coryell W, Endicott J, Maser JD, Solomon DA, Leon AC, Keller MB. A prospective investigation of the natural history of the long-term weekly symptomatic status of bipolar II disorder. Arch Gen Psychiatry. 2003 Mar;60(3):261-9. doi: 10.1001/archpsyc.60.3.261.

    PubMed 12622659

  • Gitlin MJ, Mintz J, Sokolski K, Hammen C, Altshuler LL. Subsyndromal depressive symptoms after symptomatic recovery from mania are associated with delayed functional recovery. J Clin Psychiatry. 2011 May;72(5):692-7. doi: 10.4088/JCP.09m05291gre. Epub 2010 Jun 29.

    PubMed 20673560

  • Post RM, Denicoff KD, Leverich GS, Altshuler LL, Frye MA, Suppes TM, Rush AJ, Keck PE Jr, McElroy SL, Luckenbaugh DA, Pollio C, Kupka R, Nolen WA. Morbidity in 258 bipolar outpatients followed for 1 year with daily prospective ratings on the NIMH life chart method. J Clin Psychiatry. 2003 Jun;64(6):680-90; quiz 738-9. doi: 10.4088/jcp.v64n0610.

    PubMed 12823083

  • Post RM, Leverich GS, Nolen WA, Kupka RW, Altshuler LL, Frye MA, Suppes T, McElroy S, Keck P, Grunze H, Walden J; Stanley Foundation Bipolar Network. A re-evaluation of the role of antidepressants in the treatment of bipolar depression: data from the Stanley Foundation Bipolar Network. Bipolar Disord. 2003 Dec;5(6):396-406. doi: 10.1046/j.1399-5618.2003.00065.x.

    PubMed 14636363

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bifidobacterium infantis in people with Bipolar Depression, run by Women's College Hospital at 1 site in Canada.

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 8 inclusion and 14 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: stopped early, as of the sponsor's last update on 8 Nov 2018. 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 Canada. 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. Some participants in this study may receive a placebo. 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?

The study was stopped early (reason given: The trial was terminated because of inability to recruit the needed number of participants). Results are not available in the source record.

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?

safety and tolerability of Align (time frame: 8 weeks). 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 NCT02155972, which also lists 71 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 8 Nov 2018.

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