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Trial registered on ANZCTR


Registration number
ACTRN12611000200987
Ethics application status
Approved
Date submitted
31/10/2010
Date registered
21/02/2011
Date last updated
21/02/2011
Type of registration
Retrospectively registered

Titles & IDs
Public title
Menopausal transition and prospects of treatment
Scientific title
Supplementation with alpha lipoic acid and hormone therapy with tibolone in menopausal transition: impact on oxidative stress, bone mass and quality of life.
Secondary ID [1] 252977 0
Protocol number 178/08 of Research Ethics Committee of Onofre Lopes University Hospital
Secondary ID [2] 253527 0
CAAE number 294/08
Universal Trial Number (UTN)
U1111-1117-6294
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
climacteric syndrome 261083 0
menopause 261084 0
Condition category
Condition code
Reproductive Health and Childbirth 258674 258674 0 0
Menstruation and menopause
Alternative and Complementary Medicine 258675 258675 0 0
Other alternative and complementary medicine
Metabolic and Endocrine 258676 258676 0 0
Normal metabolism and endocrine development and function

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The trial was conducted as a prospective,
randomized, placebo-controlled, double-blind. Eligible participants were randomized into four groups:
The control group(G1) - consisting of 35 participants received capsules containing placebo - microcellulose capsule;
The Tibolone Group(G2) - consisting of 30 participants received capsules containing 2.5 mg tibolone per day(Reduclin (Registered Trademark) 2.5 mg, produced by Farmoquimica S/A, Rio de Janeiro, Brazil, registered in the Ministry of health science of Brazil number 1.0390.0136-001);
The alpha lipoic acid group(G3) - consisting of 32 participants received capsules containing 600 mg of alpha lipoic acid per day;
The tibolone and alpha lipoic group(G4) consisting of 32 participants received capsules containing 2.5 mg of tibolone per day and 600 mg of alpha lipoic acid per day.
This study lasted 12 weeks. Participants were assessed at baseline, 4, 8 and 12 weeks.
Intervention code [1] 257500 0
Treatment: Drugs
Intervention code [2] 257501 0
Treatment: Other
Comparator / control treatment
Tibolone and Alpha lipoic acid for twelve weeks with daily intake of 03 capsules all identical.The type of placebo used was microcellulose capsule.
Control group
Placebo

Outcomes
Primary outcome [1] 259542 0
Climacterics Symptoms
Timepoint [1] 259542 0
The Kupperman Index(IMK) and Greene Climacteric Scale was determined at each visit. They were detected before treatement(baseline), at weeks 4 and 8(during treatment) and at week 12(end of treatment).
Primary outcome [2] 259543 0
Activity of blood antioxidant enzymes: glutathione peroxidase, superoxide dismutase, catalase and thiobarbituric acid reactive substances.
Timepoint [2] 259543 0
Glutathione peroxidase activity was determined using quantitative and qualitative characterization of erythrocyte glutathione reductase. Superoxide dismutase activity and catalase were determined spectrophotometrically. Serum thiobarbituric acid reactive substances levels were calculated using a molar absorption coefficient. They were detected before treatment(baseline) and at week 12(end of treatment).
Primary outcome [3] 259544 0
Quality of life before and after treatment.
Timepoint [3] 259544 0
Utian Quality of Life - Menopause - UQol. They were detected before treatment(baseline), at weeks 4 and 8 (during treatment) and at week 12(end of treatment).
Secondary outcome [1] 266156 0
Biochemical and hematological parameters
Timepoint [1] 266156 0
alanine aminotransferases, creatinine, triglycerides, fasting glucose, gamma-glutamyl transferase (GGT), iron, urea, total protein, albumin and Hb and C-reactive protein analyzer will be measured in 50 RA Bayer, according to the methodology specified by the manufacturers (BioSystems Reagents & Instruments). They were detected before treatment(baseline) and at week 12(end of treatment).
Secondary outcome [2] 266157 0
anthropometric assessment
Timepoint [2] 266157 0
Body mass index: ratio of weight(Kg) to the square of height(m).
Abdominal circumference(cms)
The triceps, biceps, subscapular and suprailiac be monitored by equipment Lange Skinfold Caliper, on the right side of the body.They were detected before treatment(baseline), at weeks 4 and 8 (during treatment) and at week 12(end of treatment).
Secondary outcome [3] 266158 0
Hormone assays(follicle-stimulating hormone)
Timepoint [3] 266158 0
follicle-stimulating hormone(FSH) kits (Diagnostic Products Corporation, Los Angeles, CA).
The limits of quantification FSH assays were
30 pg/ml. They were detected before treatment(baseline) and at week 12(end of treatment).
Secondary outcome [4] 266159 0
bone mineral density (BMD)
Timepoint [4] 266159 0
BMD measurements at lumbar spine
and proximal femur (femoral neck, Ward's triangle,
trochanter) were performed by dual-energy X-ray
absorptiometry (DEXA) using a scanner Brand LUNAR DPX-L Alpha Dual Energy X-Ray Bone Densitometer (Lunar Radiation Corporation, USA) and Lunar software v. 3.0. They were detected before treatment(baseline).
Secondary outcome [5] 266160 0
Mammography
Timepoint [5] 266160 0
They were detected before treatment(baseline).
Secondary outcome [6] 266165 0
transvaginal ultrasound
Timepoint [6] 266165 0
Evaluate the endometrial echoes that must be below 15 mm in baseline and after 12 weeks of treatment.

Eligibility
Key inclusion criteria
Menstrual irregularity and/ or less than 12 months amenorrhea;;
Scoring less than 14 points in the Menopausal Index Blatt and Kupperman;
Serum concentrations of FSH >30 IU/L
Minimum age
40 Years
Maximum age
55 Years
Gender
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
a)prior hormone therapy(HT) ; b) amenorrhea for more than 12 months c) early menopause(before age 40 years) or surgical menopause(hysterectomy or bilateral oophorectomy) d)the presence of systemic diseases (cardiovascular disease, diabetes, hypertension, cerebrovascular disease, thromboembolic disease, hepatic, or renal failure); e) the presence of osteoporosis; f) the presence of contraindications to HT (endometrial hyperplasia, malignant breast disease, endometrium cancer, undiagnosed vaginal bleeding); g) the presence of acute infection or chronic inflammatory disease; h)the use of drugs that could affect the metabolism (b-blockers, glucocorticoids, diuretics, lipid lowering drugs, antidiabetics, antiresorptives, anticoagulants); i) Smokers; j) the use of alcohol or drug abuse; l)Body Mass Index> 35 kg / m²; m)endometrial thickness on transvaginal ultrasound> 15 mm; n)Results of Cytopathology oncotic previous or current diagnoses of atypia of undetermined significance , high grade intraepithelial lesions, microinvasive carcinoma and cervical cancer; o)Presents some contraindication to therapy with tibolone; p) Medical conditions not listed but which may interfere with the climacteric; q) Fears, real or anticipated claims for treatment that might interfere with the objectives of the study; r)Simultaneous participation in another clinical trial.

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)
Subjects were recruited among women patients of
eight healthcare centers in the city of Parnamirim, State of Rio Grande do Norte, Brazil. The menopausal
status of the subjects was defined according to the
Stages of Reproductive Aging Workshop menstrual
criteria. This study was approved by the local Ethics
Committee (number 294/2008) and all the
women gave their informed consent prior to the inclusion in
the study. Subjects were given a short questionnaire to
obtain information about race, age, antecedents gynecological, smoking, alcohol consumption, physical exercise, previous HRT,and diagnosed diseases. The climacteric symptoms were assessed by screening the Blatt Menopausal Index (IMK). Women with case history of
alcoholism, smoking, diabetes, and chronic disease
are excluded.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The method used to create the random order for the allocation of subjects into different groups. Subjects were randomized in the ratio of 1:1, i.e.
the number of patients in the active groups was
similar of the placebo group. Randomization was performed by a central randomization who obeyed the order of selection of volunteers for input on trial.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 3004 0
Brazil
State/province [1] 3004 0
Rio Grande do Norte

Funding & Sponsors
Funding source category [1] 257964 0
Government body
Name [1] 257964 0
National Council for Scientific and Technological Development (CNPq)
Address [1] 257964 0
SEPN 507, quarto andar, sala 402
CEP 70740-901 - Brasilia
Telefone: 55 (61) 2108-9396
Country [1] 257964 0
Brazil
Primary sponsor type
University
Name
Universidade Federal do Rio Grande do Norte
Address
Street General Gustavo Cordeiro de Farias, 112- Petropolis - Natal - Rio Grande do Norte - 59012-570
Programa de Pos- Graduacao do Centro de Ciencias da Saude
Country
Brazil
Secondary sponsor category [1] 257167 0
University
Name [1] 257167 0
Universidade Potiguar
Address [1] 257167 0
NIPEC - Nucleo Integrado de Ensino, Pesquisa, Extensao e Acao Comunitaria
Avenue Aspirante Santos, 83- Santos Reis - 59.150-000 Parnamirim - RN
Country [1] 257167 0
Brazil
Secondary sponsor category [2] 257168 0
Other
Name [2] 257168 0
Prefeitura Municipal de Parnamirim
Address [2] 257168 0
Secretaria Municipal de Saude
Avenue Tenente Medeiros, 208 - Centro - 59.150-000 - Parnamirim - Rio Grande do Norte
Country [2] 257168 0
Brazil

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 259974 0
Research Ethics Committe of the Federal University of Rio Grande do Norte
Ethics committee address [1] 259974 0
Av Nilo Pecanha, 620 - Petropolis - Natal - 59012-300
Ethics committee country [1] 259974 0
Brazil
Date submitted for ethics approval [1] 259974 0
18/04/2008
Approval date [1] 259974 0
25/04/2008
Ethics approval number [1] 259974 0
2008/0294

Summary
Brief summary
To value the impact of lipoic acid supplementation and treatment with Tibolone on the condition of oxidative stress, climateric symptoms and quality of life in women in the menopausal transition.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 31844 0
Address 31844 0
Country 31844 0
Phone 31844 0
Fax 31844 0
Email 31844 0
Contact person for public queries
Name 15091 0
Maria das Gracas Almeida
Address 15091 0
Street General Cordeiro de Farias - Departamento de Farmacia - LABMULT - Laboratorio Multidisciplinar
Petropolis - 59012-570 - Natal - Rio Grande do Norte
Country 15091 0
Brazil
Phone 15091 0
55 84 99888158
Fax 15091 0
55 84 32154377
Email 15091 0
mgalmeida@digi.com.br
Contact person for scientific queries
Name 6019 0
Maria Socorro Medeiros de Morais
Address 6019 0
Avenue Governador Tarcisio de Vasconcelos Maia, 905
59065-780 - Candelaria - Natal - RN
Country 6019 0
Brazil
Phone 6019 0
55 84 99816134
Fax 6019 0
55 84 32723054
Email 6019 0
moraissos@hotmail.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary