Harms due to methamphetamine use disorder (MAUD) are rising globally. Untreated withdrawal symptoms perpetuate the cycle of dependence and are a barrier to treatment. There is no pharmacotherapy approved for methamphetamine withdrawal. Lisdexamfetamine (LDX) dimesylate has potential as an agonist therapy to ameliorate symptom severity during acute methamphetamine withdrawal and increase duration of initial abstinence and retention in treatment.

We will conduct a double-blind, randomised, controlled trial to evaluate the efficacy of LDX in reducing symptom severity during acute methamphetamine (MA) withdrawal. One hundred eighty-four adults with moderate to severe MAUD presenting to a health service requesting MA withdrawal treatment who report use of MA within the last 72 hours will be recruited. Participants will be randomised 1:1 to receive a tapering dose of lisdexamfetamine (250 mg on day 1, reducing by 50 mg per day to 50 mg on day 5, followed by 2 days of placebo washout on days 6 and 7), or placebo for 7 days. The study will be conducted over 7 days in an inpatient unit, and all participants will also receive standard inpatient withdrawal care. Participants will be followed up in the community to day 84. The primary outcome is efficacy, defined as the between-group difference in average withdrawal severity measured over the 7-day admission by the Amphetamine Withdrawal Questionnaire. Secondary outcomes are retention in treatment, treatment satisfaction, sleep and concomitant medication use (symptomatic medications and medications for other indications to day 7); safety, craving for MA, post-treatment withdrawal symptoms, depression, anxiety and stress, insomnia and cost effectiveness (to day 28) and MA use, mental, physical and social health and post-withdrawal treatment utilisation (to day 84). A First Nations qualitative substudy will assess the experiences of Aboriginal and Torres Strait Islander participants, ensuring the treatment meets the needs of First Nations people.

This protocol was first approved by the St Vincent’s Hospital Human Research Ethics Committee on 15/05/2024 (2024/ETH00788). All participants will be provided with a participant information sheet and consent form, be fully informed about the study and given ample time to consider participation. Results will be published in peer-reviewed journals and presented at national and international conferences. Findings will be presented such that individual participants will not be identifiable.

ACTRN12624001061527.

The TRAjectory of knee heaLth in runners (TRAIL) study is a prospective cohort study investigating the long-term knee health trajectories of runners with and without a heightened osteoarthritis risk. This study aims to describe the recruitment results and baseline characteristics of the TRAIL cohort.

Runners aged 18–50 years and running ≥3 times and ≥10 km per week on average in the past 6 months were eligible. Participants were recruited via running podcasts, running clubs and social media between July 2020 and August 2023. Data were collected at study enrolment and at a face-to-face baseline testing session, which occurred a median of 33 weeks (IQR 18 to 86 weeks) after enrolment. Follow-up data collection is ongoing.

Out of 462 runners who completed an online registration form, 268 runners enrolled, of which 135 had a history of knee surgery (46% females) and 133 were non-surgical controls (50% females). 60% of the surgery group had undergone anterior cruciate ligament reconstruction, 33% meniscus and/or cartilage surgery, and 7% other knee surgery. 54 participants previously enrolled were unable to continue in the study before attending baseline data collection. Of the 214 runners who remained in the study and attended baseline data collection, 108 had a history of knee surgery (49% females) and 106 did not have a history of knee surgery (51% females).

Participants will be followed for 10 years through ongoing patient-reported outcomes and continuous monitoring of training loads using wearable devices. At baseline, 4- and 10-year follow-up, knee MRI and knee-health patient-reported outcomes will be collected to evaluate structural and symptomatic knee osteoarthritis progression. Data will inform guidelines for safe running practices and rehabilitation post-knee surgery.

Current treatments for alcohol use disorders (AUD) have limited efficacy. A previous 28-day pilot trial of N-acetyl cysteine (NAC) vs placebo found NAC to be feasible and safe, with evidence of improvement on some measures of alcohol consumption. Thus, the primary aim of the NAC-AUD study is to examine the therapeutic and cost-effectiveness of NAC vs placebo in improving treatment outcomes for AUD. We will also examine the (i) effect of NAC vs placebo on mood, markers of liver injury, cognition and hangover symptoms; and (ii) predictors of any response.

This double-blind trial will randomise participants with AUD to a 12-week regimen of either NAC (2400 mg/day) or placebo. All participants will receive medical management. The primary drinking outcome will be the number of heavy drinking days (HDDs) per week, validated by phosphatidylethanol (PEth). Secondary alcohol-related outcomes will include standard drinks per drinking day (SDDD) per week and absence of any HDDs. Other secondary outcomes will include markers of liver injury, depression, anxiety, craving, hangover symptoms, cognition and blood oxidative stress markers. We will also examine the cost-efficacy of NAC vs placebo.

Ethics approval for the study has been granted by The Sydney Local Health District Ethics Review Committee (X21-0342& HREC2021/ETH11614). There are no restrictions on publication from the sponsor or other parties.

NCT05408247.