ANZCTR - Registration

Registration number

ACTRN12621001413819

Ethics application status

Approved

Date submitted

9/09/2021

Date registered

20/10/2021

Date last updated

23/09/2022

Date data sharing statement initially provided

20/10/2021

Type of registration

Prospectively registered

Titles & IDs

Public title

Assessing a live microbial therapy for the treatment of Insomnia

Scientific title

A Phase I/II Randomised, Double-Blind, Placebo-Controlled Study to Assess Safety and Efficacy of a Live Biotherapeutic Product (SVT-4A1011) in Adults with Clinically Diagnosed Insomnia

Secondary ID [1]

Nil

Universal Trial Number (UTN)

U1111-1267-1979

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Insomnia

Sleep disorder

Condition category

Condition code

Neurological

Other neurological disorders

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

The overall study duration consists of a total of 7 weeks consisting of 2 weeks of screening/baseline assessment and 5 weeks of intervention (treatment). Participants will be provided with 3 bottles of either the investigational medicine (SVT-4A1011) or Placebo at Baseline (Day 0) as an oral liquid. Participants will consume 10 mL of SVT-4A1011 or Placebo twice daily, morning and evenings for 35 Days on an empty stomach. Participants will record their adherence to the intervention in a participant diary, along with any adverse events and any concomitant medications taken during the study period. At the end of 35 Days participants will return to the clinic for assessment.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Participants will be randomised in a 1:1 ratio to receive either SVT-4A1011 or Placebo. The placebo will contain all ingredients that are in SVT-4A1011 except the bacteria, to match the IP SVT-4A1011 in smell, taste and presentation. This will consist of purified water, stevia, sodium chloride and flavour.

Control group

Placebo

Outcomes

Primary outcome [1]

To evaluate the safety and tolerability of twice daily oral consumption of SVT-4A1011 in adult participants with Insomnia, who are otherwise healthy.
Assessed by incidence of treatment emergent adverse events (TEAEs) and discontinuations due to adverse events (AEs) - determined from participant diaries and systemic vital sign tolerability:
- Blood Pressure and Heart Rate measured by using a sphygmomanometer,
- Temperature measured with a thermometer
- Respiratory rate counted by the Investigator based on number of times the chest rises in 1 minute with participant in Supine position.

Examples of known/possible adverse reactions/events:
Human safety and efficacy studies have not yet been conducted with the specific combination of bacteria species present in SVT-4A1011, however, their individual safety for human consumption is well recognised and documented. Each species has a Risk Group 1 Classification in that they are not associated with disease in healthy adults and all have been granted the Qualified Presumption of Safety (QPS) status by the European Food Safety Authority (EFSA).
Potential adverse events that participants may experience include mild gastrointestinal symptoms (including abdominal discomfort, bloating, flatulence and/or nausea), headache and/or drowsiness.

Timepoint [1]

Patient reporting and diaries reviewed at Baseline (day 0), Day 14 (mid treatment), and Day 35 (end of treatment).
Vital signs assessed at screening (day -14), Baseline (day 0) and day 35 (End of Treatment).

Primary outcome [2]

To evaluate the safety and tolerability of twice daily oral consumption of SVT-4A1011 in adult participants with Insomnia, but who are otherwise healthy. Assessed by laboratory abnormalities of blood haematological (complete blood count), biochemical parameters (electrolytes, glucose, creatinine, total protein, albumin, globulin, bilirubin, urea, urate, calcium, phosphate, magnesium) and Liver Function Tests (LFT).

Timepoint [2]

Day 0 (Baseline) and day 35 (end of treatment).

Primary outcome [3]

To evaluate the efficacy of twice daily oral consumption of SVT-4A1011 in adult participants with Insomnia, who are otherwise healthy.
Efficacy of the intervention will be assessed by the Insomnia Severity Index (ISI) questionnaire and response based on an increase/decrease of the ISI score. The ISI measures severity of both night time and day time components of Insomnia.

Timepoint [3]

Baseline (Day 0) and Day 35 (End of Treatment).

Secondary outcome [1]

To evaluate the efficacy of improving sleep quality through twice daily oral consumption of SVT-4A1011 in adult participants with Insomnia, who are otherwise healthy.
Efficacy of the intervention will be assessed objectively using the Somfit device measurement outputs. The Somfit measures a variety of sleep metrics which will be used to determine Sleep Onset Latency (SOL).

Timepoint [1]

Collected 4 nights per week for the duration of the study. Days -14 to Day -7 will serve as Baseline measurements and average weekly scores for Days 0 - Day 35 will serve as treatment measurements.

Secondary outcome [2]

To evaluate change in sleep architecture in response to twice daily oral consumption of SVT-4A1011 in adult participants with Insomnia, who are otherwise healthy.
Efficacy of the intervention will be assessed objectively using the Somfit device measurement of sleep architecture based on proportion of the night spent in the various sleep states including Rapid Eye Movement (REM) and Non-REM state (1, 2 or 3), assessed as a composite outcome.

Timepoint [2]

Collected 4 nights per week for the duration of the study. Days -14 to Day -7 will serve as Baseline measurements and average weekly scores for Days 0 - Day 35 will serve as treatment measurements.

Secondary outcome [3]

To evaluate change in rate of hourly arousal events in response to twice daily oral consumption of SVT-4A1011 in adult participants with Insomnia, who are otherwise healthy.
Efficacy of the intervention will be assessed objectively using the Somfit device measurement outputs.

Timepoint [3]

Collected 4 nights per week for the duration of the study. Days -14 to Day -7 will serve as Baseline measurements and average weekly scores for Days 0 - Day 35 will serve as treatment measurements.

Secondary outcome [4]

To evaluate the efficacy of improving sleep quality through twice daily oral consumption of SVT-4A1011 in adult participants with Insomnia, who are otherwise healthy.
Efficacy of the intervention will be assessed subjectively from patient reporting using the sleep diary. The diary measures a variety of sleep metrics and sleep habits which will be used to determine Sleep Onset Latency (SOL).

Timepoint [4]

Reported daily over 1 week of the Baseline/Screening period as a Baseline measure and daily during the final week of treatment (Days 28-35). The average score for each week will be compared between Baseline and Days 28-35.

Secondary outcome [5]

To evaluate the efficacy of twice daily oral consumption of SVT-4A1011 in adult participants with Insomnia, who are otherwise healthy.
Efficacy of the intervention will be assessed by number of study nights requiring the use of a rescue treatment, in the form of medication or supplement used to support sleep, between placebo and intervention. Use of rescue treatment will be recorded by the participant in their daily diary.

Timepoint [5]

Reported daily for the duration of the study. Days -14 to Day 0 will serve as Baseline measurements and average weekly scores for Days 0 - Day 35 will serve as treatment measurements.

Secondary outcome [6]

Change in daytime functioning through twice daily oral consumption of SVT-4A1011 in adult participants with Insomnia, who are otherwise healthy. Efficacy of the intervention will be assessed subjectively using the Work and Social Adjustment Scale (WSAS) questionnaire and response based on an increase/decrease of the WSAS score. The WSAS is a clinically validated questionnaire that measures the impact of a person's mental health difficulties on their ability to function in terms of work, home management, social leisure, private leisure and personal or family relationships.

Timepoint [6]

Baseline (Day 0) and Day 35 (End of Treatment).

Secondary outcome [7]

To evaluate the efficacy of improving quality of life through twice daily oral consumption of SVT-4A1011 in adult participants with Insomnia, who are otherwise healthy. Efficacy of the intervention will be assessed subjectively using the RAND Item 36 Short Form (SF-36) questionnaire and response based on an total and segmented increase/decrease of the SF-36 scores. The SF-36 is a clinically validated questionnaire that assesses 8 domains of health, including physical functioning, physical role, pain, general health, vitality, social function, emotional role and mental health to give quality of life measures.

Timepoint [7]

Baseline (Day 0) and Day 35 (End of Treatment).

Secondary outcome [8]

To evaluate the efficacy of improving sleep quality through twice daily oral consumption of SVT-4A1011 in adult participants with Insomnia, who are otherwise healthy.
Efficacy of the intervention will be assessed objectively using the Somfit device measurement outputs. The Somfit measures a variety of sleep metrics which will be used to determine Wake after sleep onset (WASO).

Timepoint [8]

Collected 4 nights per week for the duration of the study. Days -14 to Day -7 will serve as Baseline measurements and average weekly scores for Days 0 - Day 35 will serve as treatment measurements.

Secondary outcome [9]

To evaluate the efficacy of improving sleep quality through twice daily oral consumption of SVT-4A1011 in adult participants with Insomnia, who are otherwise healthy.
Efficacy of the intervention will be assessed objectively using the Somfit device measurement outputs. The Somfit measures a variety of sleep metrics which will be used to determine Total Sleep Time (TST).

Timepoint [9]

Collected 4 nights per week for the duration of the study. Days -14 to Day -7 will serve as Baseline measurements and average weekly scores for Days 0 - Day 35 will serve as treatment measurements.

Secondary outcome [10]

To evaluate the efficacy of improving sleep quality through twice daily oral consumption of SVT-4A1011 in adult participants with Insomnia, who are otherwise healthy.
Efficacy of the intervention will be assessed objectively using the Somfit device measurement outputs. The Somfit measures a variety of sleep metrics which will be used to determine Sleep Efficiency (SE).

Timepoint [10]

Collected 4 nights per week for the duration of the study. Days -14 to Day -7 will serve as Baseline measurements and average weekly scores for Days 0 - Day 35 will serve as treatment measurements.

Secondary outcome [11]

To evaluate the efficacy of improving sleep quality through twice daily oral consumption of SVT-4A1011 in adult participants with Insomnia, who are otherwise healthy.
Efficacy of the intervention will be assessed objectively using the Somfit device measurement outputs. The Somfit measures a variety of sleep metrics which will be used to determine number of awakenings (nWAK).

Timepoint [11]

Collected 4 nights per week for the duration of the study. Days -14 to Day -7 will serve as Baseline measurements and average weekly scores for Days 0 - Day 35 will serve as treatment measurements.

Secondary outcome [12]

To evaluate change in rate of total arousal events per night in response to twice daily oral consumption of SVT-4A1011 in adult participants with Insomnia, who are otherwise healthy.
Efficacy of the intervention will be assessed objectively using the Somfit device measurement outputs.

Timepoint [12]

Collected 4 nights per week for the duration of the study. Days -14 to Day -7 will serve as Baseline measurements and average weekly scores for Days 0 - Day 35 will serve as treatment measurements.

Secondary outcome [13]

To evaluate the efficacy of improving sleep quality through twice daily oral consumption of SVT-4A1011 in adult participants with Insomnia, who are otherwise healthy.
Efficacy of the intervention will be assessed subjectively from patient reporting using the sleep diary. The diary measures a variety of sleep metrics and sleep habits which will be used to determine Wake after sleep onset (WASO).

Timepoint [13]

Reported daily over 1 week of the Baseline/Screening period as a Baseline measure and daily during the final week of treatment (Days 28-35). The average score for each week will be compared between Baseline and Days 28-35.

Secondary outcome [14]

To evaluate the efficacy of improving sleep quality through twice daily oral consumption of SVT-4A1011 in adult participants with Insomnia, who are otherwise healthy.
Efficacy of the intervention will be assessed subjectively from patient reporting using the sleep diary. The diary measures a variety of sleep metrics and sleep habits which will be used to determine Total Sleep Time (TST).

Timepoint [14]

Reported daily over 1 week of the Baseline/Screening period as a Baseline measure and daily during the final week of treatment (Days 28-35). The average score for each week will be compared between Baseline and Days 28-35.

Secondary outcome [15]

To evaluate the efficacy of improving sleep quality through twice daily oral consumption of SVT-4A1011 in adult participants with Insomnia, who are otherwise healthy.
Efficacy of the intervention will be assessed subjectively from patient reporting using the sleep diary. The diary measures a variety of sleep metrics and sleep habits which will be used to determine Sleep Efficiency (SE).

Timepoint [15]

Reported daily over 1 week of the Baseline/Screening period as a Baseline measure and daily during the final week of treatment (Days 28-35). The average score for each week will be compared between Baseline and Days 28-35.

Secondary outcome [16]

To evaluate the efficacy of improving sleep quality through twice daily oral consumption of SVT-4A1011 in adult participants with Insomnia, who are otherwise healthy.
Efficacy of the intervention will be assessed subjectively from patient reporting using the sleep diary. The diary measures a variety of sleep metrics and sleep habits which will be used to determine number of awakenings (nWAK).

Timepoint [16]

Reported daily over 1 week of the Baseline/Screening period as a Baseline measure and daily during the final week of treatment (Days 28-35). The average score for each week will be compared between Baseline and Days 28-35.

Eligibility

Key inclusion criteria

1. Male and female Participants aged 18 to 70 years, capable of providing written informed consent and able to attend the study site on up to 4 separate occasions,
2. Insomnia Severity Index (ISI) score greater than or equal to 8 with insomnia symptoms for more than 3 times per week and present for longer than 3 months,
3. Clinical diagnosis of Insomnia determined by clinical interview conducted by a trained sleep psychologist,
4. Females of childbearing potential (FOCBP) must have a negative pregnancy test at the Baseline Visit. While on the study, FOCBP who engage in activity in which conception is possible, must use one of the approved contraceptive options described below:
a. Hormonal contraception (oral, injection, implant, transdermal patch, vaginal ring),
b. Intrauterine device (IUD),
c. Tubal Ligation,
d. Partner’s Vasectomy, or
e. Barrier method i.e., male or female condom.
5. Male Participants who have not had a vasectomy and who engage in activity in which conception is possible, must use barrier contraception i.e., male condom while on study, or if their partner is FOCBP, the partner can use hormonal contraception, an IUD or have had a tubal ligation.

Minimum age

18 Years

Maximum age

70 Years

Sex

Both males and females

Can healthy volunteers participate?

No

Key exclusion criteria

1. Sleep apnoea (AHI greater than 10) determined by PSG,
2. Medical condition, medication or sleep-related movement disorder that may be causative of the insomnia symptoms,
3. Shift-worker working hours between 10pm and 4am,
4. History of major psychiatric disorder in the past 12 months, such as severe depression, anxiety or other psychopathologic condition based on self-report or depression scores on the DASS21 greater than or equal to 21 or anxiety scores on the DASS21 greater than or equal to 15, except clinically managed mild depression,
5. History of suicide attempt, current suicide ideation or self-harm,
6. History of hypersensitivity or severe adverse reaction including but not limited to anaphylaxis to any ingredients in SVT-4A1011,
7. Skin sensitivity to adhesive or tape,
8. Use of any investigational drug and/or device within 4 weeks of screening or intent to use within the duration of the study,
9. History of any infection requiring hospitalisation, parental antimicrobial therapy, or as otherwise judged clinically significant, within the 3 months prior to screening,
10. Any prior history of septicaemia or bacteraemia,
11. Immunocompromised or those with known or suspected history of immunodeficiency,
12. Any condition that, in the opinion of the Study Coordinator or Investigators, contradicts participation in this study or poses an additional risk to the Participant including any known and /or suspected, current or recent history of uncontrolled clinically significant renal, haematological, gastrointestinal, endocrine, metabolic, pulmonary, cardiac, or neurological disease of presence of alarm systems,
13. Surgical procedure during the baseline/screening period or for the duration of the study unless deemed by the Study Coordinator to be minor and unlikely to impact on the study,
14. A Participant requiring prohibited concomitant medications including prohibited dietary supplements,
15. Females who are pregnant or breastfeeding or planning on becoming pregnant for the study period (screening and treatment),
16. Excessive caffeine or alcohol use, that in the opinion of the investigator or study delegate, contributes to the participant's insomnia,
17. Inability or unwillingness to undergo 2 venepuncture’s (e.g., because of poor tolerability or lack of access to veins),
18. Inability or unwillingness to complete the stool collection kits on 2 occasions.
19. Positive result on urine drug screen.

Study design

Statistical methods / analysis

The final ISI will be analysed with Analysis of Covariance (ANCOVA) with baseline ISI as the covariate. The null hypothesis is that mean ISI for the Treatment group is equal to mean ISI for the Placebo group. The null hypothesis will be tested against the alternative hypothesis that mean ISI for the Treatment group is not equal to mean ISI for the Placebo group. The assumptions of the ANCOVA such as normally distributed residuals, and constant variance will be assessed graphically with at least a quantile-quantile plot, and residual versus fitted plot. If necessary, rectifying transformations will be applied, or the non-parametric Wilcoxon rank sum test will be used.

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

1/02/2022

Actual

28/03/2022

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

50

Accrual to date

32

Final

Recruitment in Australia

Recruitment state(s)

QLD

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Servatus Ltd

Country [1]

Australia

Primary sponsor type

Commercial sector/Industry

Name

Servatus Ltd

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Metro North Health Human Research Ethics

Ethics committee address [1]

Building 14, The Prince Charles Hospital
Rode Road, Chermside, QLD 4032

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

09/09/2021

Approval date [1]

05/10/2021

Ethics approval number [1]

Summary

Brief summary

The aim of this study is to evaluate safety and tolerability of SVT-4A1011 as a treatment for Insomnia together with preliminary efficacy. The treatment consists of selected bacterial species that are naturally found in the digestive tract. They are a research focus for their important role in many conditions related to gut health. Bacteria play an important role in the function of the immune system, digestive health, inflammation and gut/brain axis. Several research studies have identified certain gut bacteria having direct interaction and regulation of key neurotransmitters and pathways associated with sleep including influencing the host circadian rhythm. This study will help determine how safe and effective SVT-4A1011 is as a stand-alone therapy in treating Clinically Diagnosed Insomnia. The hypothesis of this study is that, twice daily consumption of the study drug SVT-4A1011 will result in improved quality of sleep in individuals with clinically diagnosed insomnia.

Trial website

Public notes

Contacts

Principal investigator

Name

Dr Irene Szollosi

Address

Level 1, Main Building
The Prince Charles Hospital
627 Rode Road
CHERMSIDE QLD 4032

Country

Australia

Phone

+61 7 3139 6175

Email

[email protected]

Contact person for public queries

Name

Samantha Coulson

Address

Servatus Limited
14 Lomandra Place
Coolum Place, 4573
Queensland

Country

Australia

Phone

+61 7 5357 6834

Email

[email protected]

Contact person for scientific queries

Name

Irene Szollosi

Address

Level 1, Main Building
The Prince Charles Hospital
627 Rode Road
CHERMSIDE QLD 4032

Country

Australia

Phone

+61731396175

Email

[email protected]

Trial Review

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