Beyond Ageing Project: A Study for the Prevention of Depression

Beyond Ageing Project: A RCT to Assess the Benefit of Improving Mental Health Literacy as Well as the Effect of Folate and B12, and Physical Activity, in Preventing Major Depression and Cognitive Decline Among Older Australians

The purpose of this study is to determine whether folate and vitamin B12, physical activity and mental health literacy can prevent depression, and folate and vitamin B12 and physical activity can prevent cognitive impairment in older people. Also the study aims to assess the benefits for older people in improving their knowledge about mental health in relation to depression.

Study Overview

• Status: Completed
• Conditions: Depressive Disorder; Depression
• Intervention / Treatment: Drug: Folate (400mcg) and Vitamin B12 (100 mcg); Behavioral: mediated physical activity promotion; Behavioral: Mental health literacy; Drug: placebo; Behavioral: Nutrition information; Behavioral: pain and arthritis management information

Detailed Description

While preventive efforts for depression have tended to focus on adolescent and young adult populations, other stages of the lifespan also provide opportunities for prevention. With older people, there are certain risk and aetiological factors, which become more prominent and require preventive action at that point in the lifespan. The aim of this study is to determine the efficacy of various interventions in preventing depression and cognitive decline among older people who are at high risk of developing major depression because they are currently suffering from depressive symptoms.

The study has three interventions; i) folate and vitamin B12, ii) physical activity; and iii) mental health literacy. Participants will be randomly allocated to receive each combination of the interventions (folate and vitamin B12 or placebo, physical activity intervention programme or physical activity no-intervention control, mental health literacy intervention [containing written modules with information about depression that is relevant to older people] or mental health literacy no-intervention control group). Participants will receive these interventions over a two-year period with regular assessments across that time period.

• Study Type: Interventional
• Enrollment (Actual): 909
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Australian Capital Territory
    • Canberra, Australian Capital Territory, Australia, 0200
      • Australian National University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 74 years (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 65-74 years with some depressive symptoms, assessed using the Kessler 10 Psychological Distress Scale [K10] (Andrews & Slade, 2001)

Exclusion Criteria:

Any of the following:

• Those currently taking medication or receiving psychological treatment for depression
• A report of a medical diagnosis of bipolar disorder/mania
• History of epilepsy
• Diagnosed with cancer and/or on antifolate therapy
• Have a diagnosis of dementia or Alzheimer's disease
• Are currently taking vitamin supplements containing folate, B2, B6 or B12 at a dose exceeding 25% of the recommended daily intake.
• Medical contradictions to exercise (e.g., significant orthopaedic problems or cardiovascular disease that would prevent regular aerobic exercise)
• Ongoing participation in regular aerobic exercise.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Folic acid (400mcg) + Vitamin B12 (100 mcg); The vitamin intervention was a daily oral dose of one tablet consisting of folic acid 400 mcg + vitamin B12 100 mcg. The folic acid dose of 400 mcg / day was selected as it has been shown to be the dose associated with 90% of the maximal decrease in plasma homocysteine concentration for older individuals. Participants received 1 bottle x 200 tablets in six-month supplies at baseline, 6 months, 12 months, and 18 months. Adherence was monitored by telephone interviews (6 weeks, 6-, 12-, and 24 months) and 10 brief telephone tracking calls (1 - 5 weeks, and 4-, 8-, 13-, 18-, and 22-months).	Drug: Folate (400mcg) and Vitamin B12 (100 mcg); The vitamin intervention was a daily oral dose of one tablet consisting of folic acid 400 mcg + vitamin B12 100 mcg. The folic acid dose of 400 mcg / day was selected as it has been shown to be the dose associated with 90% of the maximal decrease in plasma homocysteine concentration for older individuals. Participants received 1 bottle x 200 tablets in six-month supplies at baseline, 6 months, 12 months, and 18 months. Adherence was monitored by telephone interviews (6 weeks, 6-, 12-, and 24 months) and 10 brief telephone tracking calls (1 - 5 weeks, and 4-, 8-, 13-, 18-, and 22-months).
Experimental: Mediated physical activity promotion; Individuals in the Physical Activity Promotion group received a manual designed to promote older individuals' physical activity participation to the level recommended to gain both physical and mental health benefits. The framework of the physical activity manual was informed by social cognitive theory and the transtheoretical model, and comprised five sections that reflect stages of behaviour change, including; precontemplation, contemplation, preparation, action, and maintenance. The manual contained evidence-based strategies and skills to assist people in increasing their physical activity levels. Participants received a pedometer at the commencement of the intervention as pedometry step / minute values are useful as an indicator of moderate to vigorous physical activity with total number of steps for one week recorded during the brief telephone calls at 1-5 weeks, and 4-, 8-, 13-, 18-, and 22- months.	Behavioral: mediated physical activity promotion; Individuals in the Physical Activity Promotion group received a manual designed to promote older individuals' physical activity participation to the level recommended to gain both physical and mental health benefits. The framework of the physical activity manual was informed by social cognitive theory and the transtheoretical model, and comprised five sections that reflect stages of behaviour change, including; precontemplation, contemplation, preparation, action, and maintenance. The manual contained evidence-based strategies and skills to assist people in increasing their physical activity levels. Participants received a pedometer at the commencement of the intervention as pedometry step / minute values are useful as an indicator of moderate to vigorous physical activity with total number of steps for one week recorded during the brief telephone calls at 1-5 weeks, and 4-, 8-, 13-, 18-, and 22- months.
Experimental: Mental health literacy; This MHL intervention comprised 10 modules, with nine of these specifically written for older adults. Modules 1 to 5 comprised information on depression and the evidence-based treatment for older adults. The additional MHL modules were booklets addressing evidence-based strategies and treatments for depression. It was delivered in a way to foster support and ensure that participants worked through the material systematically. Modules 1 to 5 were delivered in consecutive weeks as previous research indicates that the maximum impact of MHL on depressive symptoms may occur within the first six weeks of the intervention. Telephone interviewers contacted participants once a week for 5 consecutive weeks to motivate and support participants. There were an additional 5 check-in telephone calls, and Modules 6 to 10 of the MHL material that were delivered via postal mail at 4- (Module 6), 8- (Module 7), 13- (Module 8), 18- (Module 9), and 22- months (Module 10).	Behavioral: Mental health literacy; Comprises 10 modules, with nine of these specifically written for older adults. Modules 1 to 5 comprised information on depression and the evidence-based treatment for older adults. The additional MHL modules were booklets addressing evidence-based strategies and treatments for depression. It was delivered in a way to foster support and ensure that participants worked through the material systematically. Modules 1 to 5 were delivered in consecutive weeks as previous research indicates that the maximum impact of MHL on depressive symptoms may occur within the first six weeks of the intervention. Telephone interviewers contacted participants once a week for 5 consecutive weeks to motivate and support participants. There were an additional 5 check-in telephone calls, and Modules 6 to 10 of the MHL material that were delivered via postal mail at 4- (Module 6), 8- (Module 7), 13- (Module 8), 18- (Module 9), and 22- months (Module 10).
Placebo Comparator: Placebo tablet; A placebo tablet was the attention control intervention for the folic acid + vitamin B12 intervention group. Participants received 1 bottle x 200 tablets in 6-month supplies at baseline, 6 months, 12 months, and 18 months. Adherence was monitored by telephone interviews (6 weeks, 6-, 12-, and 24 months) and 10 brief telephone tracking calls (1 - 5 weeks, and 4-, 8-, 13-, 18-, and 22-months) during which participants counted their left-over tablets.	Drug: placebo; A placebo tablet was the attention control intervention for the folic acid + vitamin B12 intervention group. Participants received 1 bottle x 200 tablets in 6-month supplies at baseline, 6 months, 12 months, and 18 months. Adherence was monitored by telephone interviews (6 weeks, 6-, 12-, and 24 months) and 10 brief telephone tracking calls (1 - 5 weeks, and 4-, 8-, 13-, 18-, and 22-months) during which participants counted their left-over tablets.; Other Names: placebo tablet
Active Comparator: Nutrition information; The attention control intervention for the physical activity intervention was printed nutrition literacy and included information concerning the recommended dietary guidelines for older Australians, as well as strategies and additional information to facilitate beneficial dietary behaviours. The same procedure was adhered to as the physical activity intervention to ensure adequate attention control. Participants in the nutrition promotion intervention received 5 brief telephone calls from an interviewer to facilitate adherence to the intervention, and to offer support and clarification of the materials. Participants received five further brief telephone calls as well as nutrition newsletters that were delivered via postal mail at 4-, 8-, 13-, 18-, and 22- months.	Behavioral: Nutrition information; The attention control intervention for the physical activity intervention was printed nutrition literacy and included information concerning the recommended dietary guidelines for older Australians, as well as strategies and additional information to facilitate beneficial dietary behaviours. The same procedure was adhered to as the physical activity intervention to ensure adequate attention control. Participants in the nutrition promotion intervention received 5 brief telephone calls from an interviewer to facilitate adherence to the intervention, and to offer support and clarification of the materials. Participants received five further brief telephone calls as well as nutrition newsletters that were delivered via postal mail at 4-, 8-, 13-, 18-, and 22- months.
Active Comparator: Pain and arthritis management information; Pain and Arthritis Information was used as the attention control intervention for the MHL intervention and comprised 10 modules. Modules 1 to 5 were contained in an Arthritis Australia consumer guide for arthritis management. Modules 6 to 10 were a series of information pamphlets on pain management, osteoporosis and falls prevention. The delivery of the Pain Information was identical to the MHL intervention with Modules 1 to 5 distributed via postal mail in five consecutive weeks (1-5 weeks), while the remaining intervention modules were delivered at 4- (Module 6), 8- (Module 7), 13- (Module 8), 18- (Module 9), and 22- months (Module 10). Participants also received 10 brief calls from a telephone interviewer that coincided with receiving the print intervention materials.	Behavioral: pain and arthritis management information; Pain and Arthritis Information was used as the attention control intervention for the MHL intervention and comprised 10 modules. Modules 1 to 5 were contained in an Arthritis Australia consumer guide for arthritis management. Modules 6 to 10 were a series of information pamphlets on pain management, osteoporosis and falls prevention. The delivery of the Pain Information was identical to the MHL intervention with Modules 1 to 5 distributed via postal mail in five consecutive weeks (1-5 weeks), while the remaining intervention modules were delivered at 4- (Module 6), 8- (Module 7), 13- (Module 8), 18- (Module 9), and 22- months (Module 10). Participants also received 10 brief calls from a telephone interviewer that coincided with receiving the print intervention materials.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Depression	The Patient Health Questionnaire - 9 (PHQ - 9) is a brief self-administered diagnostic instrument for depressive symptoms with items derived from the nine diagnostic criteria for Major Depression Disorder using the DSM - IV. The items are coded "0" (not at all) to "3" (nearly every day) for the most recent 2-week period, with possible scores ranging from 0 to 27, higher scores indicating greater depression severity. The PHQ - 9 is used in research and clinical settings, and can be administered via telephone. Studies support its reliability, validity, and ability to detect change over time.	Baseline, 6 weeks, 6-, 12-, 48-, and 51 month followups.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physical activity level	The International Physical Activity Questionnaire - Short Form (IPAQ - SF) was used as a self-report measure of physical activity. The purpose of the IPAQ is to survey physical activity in large groups or populations. The IPAQ allows for a total of metabolic equivalent (MET) units expended in the most recent seven-day period.	Baseline, 6 weeks, 6-, 12-, 48-, and 51 month followups.
Cognitive impairment	The modified Telephone Interview of Cognitive Status has a max. total score= 39, and comprises 4 domains: orientation; recent memory and delayed recall; attention; and, semantic memory. It has excellent discrimination in cognitive performance in the general population. Processing speed was measured (Brief Test of Adult Cognition-Telephone) with the task to count backwards quickly from 100 by 1's for 30 seconds The Informant Questionnaire on Cognitive Decline in the Elderly was given at 2yr FU to a person who had known the participant for > 2yrs. It measures cognitive decline and dementia.	Baseline, 12-, and 48-month followups.
Physical health outcomes	A health checklist was given to determine current health status with items addressing the following health domains: cardiovascular, pulmonary, musculoskeletal, psychiatric, vision, and renal health; cancer, diabetes, and epilepsy. Blood collections were also used at baseline, 12- and 24 months to further investigate health including: thyroid stimulating hormone; liver and kidney function; fasting cholesterol and blood glucose; C-reactive protein; and haematological parameters.	Baseline, 6-week, 6-, 12-, 24-, and 48-month followups.
B12 levels	Serum vitamin B12 was measured using chemiluminscent microparticle assays (Architect i2000, Abbott Laboratories). This allowed a check on whether participants were taking the supplements, and to initially to comply with inclusion/exclusion criteria.	Baseline, 12-, and 48-month followups.
Folate status	Red cell folate was measured using chemiluminscent microparticle assays (Architect i2000, Abbott Laboratories). This allowed a check on whether participants were taking the supplements, and as part of the initial screening process to comply with our inclusion/exclusion criteria.	Baseline, 12-, and 48-month followups.
Homocysteine	A fluorescence polarization immunoassay was used for the quantitative determination of total L-homocysteine in plasma (AxSYM, Abbott Laboratories). This allowed us to establish any changes in Hcy concentration.	Baseline, 12- and 24-month followups.

Collaborators and Investigators

• Sponsor: Australian National University
• Collaborators: University of Sydney; Commonwealth Scientific and Industrial Research Organisation, Australia; Australian Government Department of Health and Ageing
• Investigators: Principal Investigator: Professor Helen Christensen, PhD, Centre for Mental Health Research, ANU; Principal Investigator: Professor Anthony F Jorm, PhD, ORYGEN Research Centre, University of Melbourne; Principal Investigator: Professor Ian Hickie, PhD, Brain and Mind Research Institute, University of Sydney; Principal Investigator: Dr Janine G Walker, PhD, Centre for Mental Health Research, Australian National University, Canberra, Australia

Publications and helpful links

General Publications

• Walker JG, Batterham PJ, Mackinnon AJ, Jorm AF, Hickie I, Fenech M, Kljakovic M, Crisp D, Christensen H. Oral folic acid and vitamin B-12 supplementation to prevent cognitive decline in community-dwelling older adults with depressive symptoms--the Beyond Ageing Project: a randomized controlled trial. Am J Clin Nutr. 2012 Jan;95(1):194-203. doi: 10.3945/ajcn.110.007799. Epub 2011 Dec 14. Erratum In: Am J Clin Nutr. 2012 Aug;96(2):448. Dosage error in article text.
• Christensen H, Aiken A, Batterham PJ, Walker J, Mackinnon AJ, Fenech M, Hickie IB. No clear potentiation of antidepressant medication effects by folic acid+vitamin B12 in a large community sample. J Affect Disord. 2011 Apr;130(1-2):37-45. doi: 10.1016/j.jad.2010.07.029.
• Walker JG, Mackinnon AJ, Batterham P, Jorm AF, Hickie I, McCarthy A, Fenech M, Christensen H. Mental health literacy, folic acid and vitamin B12, and physical activity for the prevention of depression in older adults: randomised controlled trial. Br J Psychiatry. 2010 Jul;197(1):45-54. doi: 10.1192/bjp.bp.109.075291.

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: September 14, 2005
• First Submitted That Met QC Criteria: September 14, 2005
• First Posted (Estimate): September 22, 2005

Study Record Updates

• Last Update Posted (Estimate): September 13, 2011
• Last Update Submitted That Met QC Criteria: September 12, 2011
• Last Verified: September 1, 2011

More Information

Terms related to this study

• Keywords: Depression; Cognition; Older adults; Depressive disorder; Mental health literacy; Randomzed controlled trial
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Hematinics; Vitamin B 12; Hydroxocobalamin
• Other Study ID Numbers: 2004/188 HREC; 2005/483 (TGA)