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Trial registered on ANZCTR


Registration number
ACTRN12613001363774
Ethics application status
Approved
Date submitted
6/11/2013
Date registered
12/12/2013
Date last updated
12/01/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
A double-blind placebo-controlled trial of a Lactium and Zizyphus complex for sleep
Scientific title
A double-blind placebo-controlled trial of a Lactium and Zizyphus complex for sleep
Secondary ID [1] 283497 0
Nil
Universal Trial Number (UTN)
U1111-1149-3113
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Poor quality sleep 290416 0
Condition category
Condition code
Neurological 290807 290807 0 0
Other neurological disorders
Alternative and Complementary Medicine 290985 290985 0 0
Herbal remedies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Lactium and Zizyphus complex, LZ Complex3 a herb and supplement complex, 2 tablets (1600mg/tab) daily before retiring for sleep, for 14 days.

Drug tablet return; Daily completion of participant diary; compliance check at clinic visits.
Intervention code [1] 288204 0
Treatment: Drugs
Comparator / control treatment
Placebo (Isomalt) 2 tablets daily before retiring for sleep, for 14 days.
Control group
Placebo

Outcomes
Primary outcome [1] 290801 0
Primary Outcome: To assess overall sleep quality using the Pittsburgh Sleep Quality Index (PSQI) in healthy adults experiencing sleep problems.
Timepoint [1] 290801 0
on days 8, 9, 11, 15, 22 and 29.
Secondary outcome [1] 305323 0
To assess overall sleep quality using: Leeds Sleep Evaluation Questionnaire (LSEQ); Epworth Sleepiness Scale (ESS); Insomnia Severity Index (ISS) and a Daily Sleep Diary
Timepoint [1] 305323 0
LSEQ, ESS & ISS on days 8, 9, 11, 15, 22 and 29. Daily Sleep Diary: Day1 through to Day 22.
Secondary outcome [2] 305324 0
To assess daytime functioning and physical fatigue using: Chalder Fatigue Scale and the Burckhardt Quality of Life scale.
Timepoint [2] 305324 0
Timepoints: on days 8, 9, 11, 15, 22 and 29.
Secondary outcome [3] 305325 0
To assess mood and anxiety using composite scores from: Bond-Lader, STAI-S, Stress & Fatigue Visual Analogue Mood Scales and cognitive performance Purple Multi-tasking framework.
Timepoint [3] 305325 0
Mood timepoints: on days 8, 9, 11, 15, 22 and 29.
Anxiety timepoints: on days 8, 9, 11, 15, 22 and 29.
Cognitive Performance Timepoints: on days 8, 22 and 29.
Secondary outcome [4] 305326 0
To assess stress reactivity using: Bond-Lader Visual Analogue Scales and the State-Trait Anxiety Inventory (STAI-s) for Adults and Fatigue Visual Analogue Mood scales.
Timepoint [4] 305326 0
Timepoints: on days on days 8, 22 and 29.
Secondary outcome [5] 305327 0
To assess the safety of LZ Complex3 in this population using:
Adverse Event reporting.
Timepoint [5] 305327 0
Timepoint: from entering the study until the end of study visit (visit 4 / day 29).
Secondary outcome [6] 310970 0
To assess post treatment effects of all secondary outcomes using: Leeds Sleep Evaluation Questionnaire (LSEQ); Epworth Sleepiness Scale (ESS); Insomnia Severity Index (ISS);Chalder Fatigue Scale and the Burckhardt Quality of Life scale; Bond-Lader Visual Analogue Scales; Fatigue Visual Analogue Mood scales; State-Trait Anxiety Inventory (STAI-s) and the PURPLE multitasking framework.
Timepoint [6] 310970 0
To assess the post treatment effects up to 1 week following 2 weeks of treatment from the end of treatment Visit 3 on Day 22 to the follow-up Visit 4 on Day 29.
Secondary outcome [7] 310971 0
Exploratory Objective, sleep quality using Actigraphy to explore cross-validation of endpoints
Timepoint [7] 310971 0
From D8 to D29

Eligibility
Key inclusion criteria
I01. Individuals with no significant diagnosed diseases by the judgment of the Investigator, who self-report sleeping difficulties over a 1 month prior to the screening call.
I02. Age range 18-65 years
I03. Body Mass Index 18-30 kg/m2
I04. Normal vital signs
I05. Pittsburgh Sleep Quality Index Score greater than 5.
I06. Typical bedtime between 9 pm and 12 am.
I07. Symptoms consistent with Primary Insomnia established at screening.
I08. Signed written informed consent
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
E01. Hospital Depression and Anxiety Scale (HADS) depression score greater than 8 and/or anxiety score greater than 12 (assessed at screening)
E02. Regular use of illicit drugs, excessive or inappropriate use of over the counter (OTC) or prescription drugs or excessive use of alcohol (assessed by the Investigator or delegate and/or reported by the potential participant)
E03. Smoking more than 10 cigarettes a day
E04. Consumption of stimulants: more than 10 cups of tea or coffee (or equivalent of other caffeine containing drinks), thus exceeding an intake of more than 2 litres a day and/or consumption of these drinks after 5 p.m.
E05. Allergy to milk proteins, latex or LZ Complex 3 ingredients
E06. Subjects with a primary sleep disorder (sleep apnoea-hypopnoea, periodic limb movement disorder, restless legs syndrome, narcolepsy, idiopathic hypersomnia, Kleine-Levin syndrome)
E07. Use of medicinal products for sleep disorders (e.g. hypnotic agents, anxiolytics, herbal remedies, homeopathy for hypnotic purposes) in the month prior to inclusion, or exhibiting withdrawal symptoms from the use of medicinal products for sleep disorders at screening.
E08. On-going non-pharmacological treatment of sleep disorders (e.g. cognitive behavioural therapy, relaxation therapy)
E09. Expected sleep disturbance from external sources during the study period (such as young children or other household disturbance).
E10. Previous failure on prescription sleep medication
E11. Pregnancy or lactation
E12. Current sleep disturbance due to pain or a general medical condition including but not limited to Pain, Cystitis, Urinary frequency, Heart burn or others by the judgment of the Investigator would preclude participation in the study.
E13. Sleep Efficiency greater than 85% AND Sleep Onset Latency below 31 minutes AND Wake after Sleep Onset below 31 minutes (assessed during week 1 using the Consensus Sleep Diary).
E14. Participants who withdraw consent during screening (participants who are not willing to continue or fail to return).

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Numbered treatment kits, manually assigned.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation
Created by SAS (statistical software)
Checked by programmer and independent statistician
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Saint-Hilaire et al (2009) conducted a trial of Lactium and found a difference between active and placebo which emerged after 14 days and was most evident at 28 days. The study used parametric statistics and presents medians and ranges. However it is possible to use these to estimate effect size drawing on the methodology of Hozo et al 2005. These provide effect sizes of approximately 0.4 and 0.65 at day 14 and 28 respectively. We suggest that the effect size for LZ Complex3 will be similar to the day 28 value for the following reasons: the addition of other active ingredients which may summate or act synergistically with lactium and the use of a placebo run-in which will effectively screen out placebo responders.
The following calculation is based on the assumption that there will be an effect size of around 0.5 i.e. a medium effect size (0.5). We predict that there will be an advantage for LZ Complex3 so the calculation is based on a one-tailed test with 80% power to detect a change at the a equals 5% level (see output below):

t tests - Means: Difference between two independent means (two groups)
Analysis: A priori: Compute required sample size
Input: Tail(s) equals Two
Effect size d equals 0.5
a err prob equals 0.05
Power (1-Beta err prob) equals 0.8
Allocation ratio N2/N1 equals 1

Output: Noncentrality parameter d equals 2.8284271
Critical t equals 1.9789706
Df equals 126
Sample size group 1 equals 64
Sample size group 2 equals 64
Total sample size equals 128
Actual power equals 0.8014596

The required number of participants for each treatment arm is calculated at 64.
To account for 33% of patient dropouts/non-compliance, the total number of participants to be included in the two week double-blind randomised treatment period will be 170.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
16/12/2013
Actual
6/01/2014
Date of last participant enrolment
Anticipated
30/01/2015
Actual
2/12/2014
Date of last data collection
Anticipated
Actual
Sample size
Target
170
Accrual to date
Final
171
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 7525 0
3122 - Hawthorn

Funding & Sponsors
Funding source category [1] 288197 0
Commercial sector/Industry
Name [1] 288197 0
Sanofi Consumer Healthcare pty ltd
(sanofi-aventis group)
Country [1] 288197 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Sanofi Australia pty ltd
Address
Talavera Corporate Centre
Building D, 12-24 Talavera Road
Macquarie Park, NSW 2113
Country
Australia
Secondary sponsor category [1] 286923 0
None
Name [1] 286923 0
Address [1] 286923 0
Country [1] 286923 0
Other collaborator category [1] 277680 0
University
Name [1] 277680 0
Swinburne University
Address [1] 277680 0
Centre for Human Psychopharmacology
Swinburne University
ATC 1009, Mail H24, PO Box 218
Hawthorn
Victoria, 3122
AUSTRALIA
Country [1] 277680 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290109 0
Bellberry Ltd.
Ethics committee address [1] 290109 0
Ethics committee country [1] 290109 0
Australia
Date submitted for ethics approval [1] 290109 0
17/04/2013
Approval date [1] 290109 0
30/09/2013
Ethics approval number [1] 290109 0
2013-04-174

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 44014 0
Prof Andrew Scholey
Address 44014 0
Director, Centre for Human Psychopharmacology
ATC 1009, Mail H24, PO Box 218
Swinburne University
Melbourne
VIC, 3122
AUSTRALIA
Country 44014 0
Australia
Phone 44014 0
+6139214 8932
Fax 44014 0
+6139214 5525
Email 44014 0
andrew@scholeylab.com
Contact person for public queries
Name 44015 0
Rebekah Miles
Address 44015 0
Head of Communications Consumer Healthcare
Sanofi Consumer Healthcare
87 Yarraman Place
Virginia
QLD, 4014
Country 44015 0
Australia
Phone 44015 0
+61732128794
Fax 44015 0
Email 44015 0
Rebekah.Miles@sanofi.com
Contact person for scientific queries
Name 44016 0
Amanda Smith
Address 44016 0
Manager Research – Product Innovation
Sanofi Consumer Healthcare
87 Yarraman Place
Virginia
QLD, 4014
Country 44016 0
Australia
Phone 44016 0
+61732128670
Fax 44016 0
Email 44016 0
Amanda.Smith4@sanofi.com

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseExploring the effect of lactiumTM and zizyphus complex on sleep quality: A double-blind, randomized placebo-controlled trial.2017https://dx.doi.org/10.3390/nu9020154
N.B. These documents automatically identified may not have been verified by the study sponsor.