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A multicenter, blinded, randomized, factorial controlled trial of doxycycline and rifampin for treatment of Alzheimer's disease: the DARAD trial
Molloy DW, Standish TI, Zhou Q, Guyatt G, DARAD Study Group.. International journal of geriatric psychiatry, 2012-06-21
Topic: Amyloid, tau and blood-test diagnosis
Objectives Preliminary evidence suggested that doxycycline and rifampin might stop or slow the progression of Alzheimer's disease (AD). We carried out a randomized trial to confirm or refute these findings. Methods A multicenter, blinded, randomized, 2 × 2 factorial controlled trial, set at 14 geriatric outpatient clinics in Canada. Four hundred and six patients with mild to moderate AD (standardized mini mental state examination (SMMSE) score 14-26) participated. The intervention was 12 months' treatment with doxycycline 100 mg twice daily + rifampin 300 mg daily or doxycycline 100 mg twice daily + placebo-rifampin daily or rifampin 300 mg daily + placebo-doxycycline twice daily or placebo-doxycycline twice daily + placebo-rifampin daily. Coprimary outcomes were the Standardized Alzheimer's Disease Assessment Scale-Cognitive Subscale (SADAS-cog) and the Clinical Dementia Rating Scale-Sum of the Boxes (CDR-SB). Secondary outcomes were the SMMSE, Quick mild cognitive impairment screen, Geriatric Depression Scale, Cornell Scale for Depression in Dementia, activities of daily living (Lawton Scale), and the Dysfunctional Behavior Rating Instrument frequency and reaction subscales. Results There was a significant deterioration in SADAS-cog over time with both rifampin and doxycycline in comparison with placebo. When the two were used together, there was no statistically significant decline/deterioration in comparison with placebo (n = 305). For the CDR-SB, there were no significant effects of either rifampin or doxycycline. Secondary outcome results followed similar patterns. Conclusion Twelve months' treatment with doxycycline or rifampin, alone or in combination, has no beneficial effects on cognition or function in AD.
Key findings
- Objectives Preliminary evidence suggested that doxycycline and rifampin might stop or slow the progression of Alzheimer's disease (AD).
- We carried out a randomized trial to confirm or refute these findings.
- Results There was a significant deterioration in SADAS-cog over time with both rifampin and doxycycline in comparison with placebo.
- When the two were used together, there was no statistically significant decline/deterioration in comparison with placebo (n = 305).
- For the CDR-SB, there were no significant effects of either rifampin or doxycycline.
Why it matters
In this randomized trial of 406 patients with mild to moderate Alzheimer's disease, there was significant deterioration on a cognitive scale over time with both rifampin and doxycycline compared with placebo, and no statistically significant decline when the two were used together. The trial did not confirm the preliminary suggestion that these antibiotics slow or stop Alzheimer's disease progression.
Study details
- Study designrandomized controlled trial
- Participants305
- Evidence strengthHigh
How this study scored 64/100
Published in a peer-reviewed journal, and it is a randomised controlled trial. Scored zero for effect reported because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 61 of the 96 points we could judge it on, which is 64 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (International journal of geriatric psychiatry) |
| Journal's citation record | 2 / 4 | International Journal of Geriatric Psychiatry: journal h-index 190 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A randomised controlled trial |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2013 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 305 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 2 / 2 | Randomised and blinded or placebo-controlled (as stated in the record) |
| Times cited | 5 / 7 | Cited 128 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 8.5 citations a year over 15 year(s) since 2013 |
| Impact for its field and year | 2 / 6 | Cited 1.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 2 / 4 | Cited 27 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 1 / 3 | McMaster University: institution h-index 1,334 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 22718435) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 61 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 61 of the 96 points we could judge it on is 64 out of 100. |
| Total | 64 / 100 | — |
What each of these 20 components measures, and what this score is not →
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Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Molloy, D. W., Standish, T. I., Zhou, Q., Guyatt, G., & DARAD Study Group. (2013). A multicenter, blinded, randomized, factorial controlled trial of doxycycline and rifampin for treatment of Alzheimer's disease: the DARAD trial. International journal of geriatric psychiatry. https://doi.org/10.1002/gps.3846
Vancouver
Molloy DW, Standish TI, Zhou Q, Guyatt G, DARAD Study Group. A multicenter, blinded, randomized, factorial controlled trial of doxycycline and rifampin for treatment of Alzheimer's disease: the DARAD trial. International journal of geriatric psychiatry. 2013. doi:10.1002/gps.3846. PMID: 22718435.
BibTeX
@article{molloy2013-22718435,
author = {Molloy, D. W. and Standish, T. I. and Zhou, Q. and Guyatt, G. and {DARAD Study Group}},
title = {{A multicenter, blinded, randomized, factorial controlled trial of doxycycline and rifampin for treatment of Alzheimer's disease: the DARAD trial}},
journal = {International journal of geriatric psychiatry},
year = {2013},
doi = {10.1002/gps.3846},
pmid = {22718435},
url = {https://doi.org/10.1002/gps.3846}
}
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